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### /home/biocbuild/bbs-3.20-bioc/R/bin/R CMD build --keep-empty-dirs --no-resave-data SomaScan.db
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* checking for file ‘SomaScan.db/DESCRIPTION’ ... OK
* preparing ‘SomaScan.db’:
* checking DESCRIPTION meta-information ... OK
* installing the package to build vignettes
* creating vignettes ... ERROR
--- re-building ‘SomaScan-db.Rmd’ using rmarkdown
--- finished re-building ‘SomaScan-db.Rmd’
--- re-building ‘advanced_usage_examples.Rmd’ using rmarkdown
Quitting from advanced_usage_examples.Rmd:248-254 [get-path-names]
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<error/rlang_error>
Error in `if (.self$lastField == "REFERENCE") ...`:
! missing value where TRUE/FALSE needed
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Backtrace:
▆
1. ├─stats::setNames(keggGet(dbentries = hsa_names), hsa_names[1:10L])
2. └─KEGGREST::keggGet(dbentries = hsa_names)
3. └─KEGGREST:::.getUrl(url, .flatFileParser)
4. ├─base::do.call(parser, list(content, ...))
5. └─KEGGREST (local) `<fn>`("ENTRY hsa04514 Pathway\nNAME Cell adhesion molecules - Homo sapiens (human)\nDESCRIPTION Cell adhesion molecules (CAMs) are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, embryogenesis, and development of neuronal tissue. There are four main groups: the integrin family, the immunoglobulin superfamily, selectins, and cadherins. Membrane proteins that mediate immune cell–cell interactions fall into different categories, namely those involved in antigen recognition, costimulation and cellular adhesion. Furthermore cell-cell adhesions are important for brain morphology and highly coordinated brain functions such as memory and learning. During early development of the nervous system, neurons elongate their axons towards their targets and establish and maintain synapses through formation of cell-cell adhesions. Cell-cell adhesions also underpin axon-axon contacts and link neurons with supporting schwann cells and oligodendrocytes.\nCLASS Environmental Information Processing; Signaling molecules and interaction\nPATHWAY_MAP hsa04514 Cell adhesion molecules\nDRUG D02800 Alefacept (USAN/INN)\n D02811 Alicaforsen sodium (USAN)\n D02967 Apolizumab (USAN/INN)\n D03066 Bectumomab (USAN/INN)\n D03114 Bimosiamose disodium (USAN)\n D03203 Abatacept (USAN/INN)\n D03222 Belatacept (USAN/INN)\n D03420 Cedelizumab (USAN/INN)\n D03497 Cilengitide (USAN/INN)\n D03959 Efalizumab (USAN/INN)\n D04000 Enlimomab (USAN/INN)\n D04036 Epratuzumab (USAN/INN)\n D04045 Erlizumab (USAN/INN)\n D04295 Galiximab (USAN/INN)\n D05610 Priliximab (USAN/INN)\n D05777 Ruplizumab (USAN/INN)\n D05847 Siplizumab (USAN/INN)\n D06071 Teneliximab (USAN/INN)\n D06194 Torapsel (USAN/INN)\n D06348 Yttrium Y 90 epratuzumab (USAN)\n D06349 Yttrium Y 90 epratuzumab tetraxetan (USAN)\n D06356 Zanolimumab (USAN/INN)\n D06570 Camobucol (USAN/INN)\n D06582 Elsibucol (USAN/INN)\n D06590 Firategrast (USAN)\n D06648 Succinobucol (USAN)\n D06657 Tremelimumab (USAN/INN)\n D08083 Vedolizumab (USAN)\n D08933 Inotuzumab ozogamicin (USAN/INN)\n D09575 Ibalizumab (USAN/INN)\n D09631 Intetumumab (USAN/INN)\n D09799 Carotegrast methyl (JAN)\n D09927 Lorvotuzumab mertansine (USAN/INN)\n D09929 Maraciclatide (USAN/INN)\n D09932 Moxetumomab pasudotox (USAN/INN)\n D10028 Valategrast hydrochloride (USAN)\n D10316 Nivolumab (USAN/INN)\n D10374 Lifitegrast (USAN/INN)\n D10390 Pidilizumab (USAN/INN)\n D10392 Lifitegrast sodium (USAN)\n D10574 Pembrolizumab (USAN)\n D10773 Atezolizumab (USAN/INN)\n D10808 Durvalumab (USAN/INN)\n D10817 Avelumab (USAN/INN)\n D11108 Cemiplimab (USAN)\n D11310 Uproleselan sodium (USAN)\n D11332 Uproleselan (USAN/INN)\n D11357 Bleselumab (USAN/INN)\n D11366 Dostarlimab (USAN)\n D11433 Vopratelimab (USAN/INN)\n D11480 Crizanlizumab (USAN/INN)\n D11482 Tiragolumab (USAN/INN)\n D11487 Tislelizumab (USAN/INN)\n D11488 Cetrelimab (USAN/INN)\n D11491 Selicrelumab (USAN/INN)\n D11515 Omburtamab (USAN/INN)\n D11527 Zolbetuximab (USAN/INN)\n D11532 Lodapolimab (USAN)\n D11593 Etigilimab (USAN/INN)\n D11597 Ravagalimab (USAN/INN)\n D11605 Spartalizumab (USAN/INN)\n D11610 Iscalimab (USAN/INN)\n D11747 Inbakicept (USAN/INN)\n D11752 Enoblituzumab (USAN/INN)\n D11795 Vibostolimab (USAN/INN)\n D11820 Balstilimab (USAN/INN)\n D11827 Retifanlimab (USAN)\n D11893 Bintrafusp alfa (USAN/INN)\n D11907 Rozibafusp alfa (USAN/INN)\n D11919 Fuzapladib sodium hydrate (JAN)\n D11930 Betibeglogene autotemcel (USAN/INN)\n D11946 Cosibelimab (USAN/INN)\n D11948 Pacmilimab (USAN/INN)\n D11959 Praluzatamab (USAN/INN)\n D11996 Feladilimab (USAN/INN)\n D12063 Zimberelimab (USAN)\n D12119 Sintilimab (USAN/INN)\n D12143 Pimivalimab (USAN)\n D12154 Mirzotamab (USAN/INN)\n D12178 Sotigalimab (USAN)\n D12186 Vudalimab (USAN)\n D12190 Cadonilimab (USAN/INN)\n D12195 Izuralimab (USAN)\n D12198 Penpulimab (USAN)\n D12202 Toripalimab (USAN/INN)\n D12223 Rosnilimab (USAN)\n D12231 Peresolimab (USAN)\n D12233 Quavonlimab (USAN/INN)\n D12283 Ociperlimab (USAN/INN)\n D12300 Acazicolcept (USAN/INN)\n D12317 Bavunalimab (USAN/INN)\n D12332 Zeluvalimab (USAN/INN)\n D12344 Socazolimab (USAN)\n D12347 Volrustomig (USAN)\n D12348 Belrestotug (USAN)\n D12349 Danburstotug (USAN)\n D12367 Domvanalimab (USAN/INN)\n D12426 Itolizumab (USAN/INN)\n D12448 Botensilimab (USAN/INN)\n D12463 Davoceticept (USAN/INN)\n D12517 Vobramitamab (USAN/INN)\n D12518 Voramitamab duocarmazine (USAN/INN)\n D12592 Omidubicel (USAN)\n D12620 Frexalimab (USAN/INN)\n D12722 Bexotegrast (USAN/INN)\n D12749 Exagamglogene autotemcel (USAN/INN)\n D12750 Sugemalimab (INN)\n D12751 Serplulimab (USAN/INN)\n D12753 Ifinatamab deruxtecan (USAN/INN)\n D12764 Rilvegostomig (USAN/INN)\n D12765 Lovotibeglogene autotemcel (USAN/INN)\n D12781 Osemitamab (USAN/INN)\n D12839 Sasanlimab (USAN/INN)\n D12877 Atidarsagene autotemcel (USAN/INN)\n D12926 Puxitatug (USAN/INN)\n D12927 Puxitatug samrotecan (USAN/INN)\n D12961 Tobemstomig (USAN/INN)\n D12997 Lixudebart (USAN/INN)\n D13000 Dargistotug (USAN/INN)\n D13005 Vilastobart (USAN/INN)\n D13033 Abiprubart (USAN/INN)\n D13064 Gotistobart (USAN/INN)\n D13070 Ifinatamab (USAN/INN)\n D13087 Trosunilimab (USAN/INN)\nDBLINKS GO: 0050839\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 1000 CDH2; cadherin 2 [KO:K06736]\n 1001 CDH3; cadherin 3 [KO:K06796]\n 100132463 CLDN24; claudin 24 [KO:K06087]\n 1002 CDH4; cadherin 4 [KO:K06797]\n 100288814 CLDN34; claudin 34 [KO:K06087]\n 1003 CDH5; cadherin 5 [KO:K06533]\n 100506658 OCLN; occludin [KO:K06088]\n 1013 CDH15; cadherin 15 [KO:K06809]\n 102723996 [KO:K06710]\n 10666 CD226; CD226 molecule [KO:K06567]\n 10686 CLDN16; claudin 16 [KO:K06087]\n 114798 SLITRK1; SLIT and NTRK like family member 1 [KO:K25832]\n 120425 JAML; junction adhesion molecule like [KO:K28137]\n 1272 CNTN1; contactin 1 [KO:K06759]\n 1364 CLDN4; claudin 4 [KO:K06087]\n 1365 CLDN3; claudin 3 [KO:K06087]\n 1366 CLDN7; claudin 7 [KO:K06087]\n 137075 CLDN23; claudin 23 [KO:K06087]\n 139065 SLITRK4; SLIT and NTRK like family member 4 [KO:K25835]\n 1462 VCAN; versican [KO:K06793]\n 1493 CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]\n 149461 CLDN19; claudin 19 [KO:K06087]\n 152404 IGSF11; immunoglobulin superfamily member 11 [KO:K06791]\n 1525 CXADR; CXADR Ig-like cell adhesion molecule [KO:K06788]\n 201633 TIGIT; T cell immunoreceptor with Ig and ITIM domains [KO:K16350]\n 214 ALCAM; activated leukocyte cell adhesion molecule [KO:K06547]\n 22829 NLGN4Y; neuroligin 4 Y-linked [KO:K07378]\n 22854 NTNG1; netrin G1 [KO:K07522]\n 22865 SLITRK3; SLIT and NTRK like family member 3 [KO:K25834]\n 22871 NLGN1; neuroligin 1 [KO:K07378]\n 23114 NFASC; neurofascin [KO:K06757]\n 23308 ICOSLG; inducible T cell costimulator ligand [KO:K06710]\n 23562 CLDN14; claudin 14 [KO:K06087]\n 23705 CADM1; cell adhesion molecule 1 [KO:K06781]\n 24146 CLDN15; claudin 15 [KO:K06087]\n 257194 NEGR1; neuronal growth regulator 1 [KO:K06775]\n 25945 NECTIN3; nectin cell adhesion molecule 3 [KO:K06592]\n 26047 CNTNAP2; contactin associated protein 2 [KO:K07380]\n 26050 SLITRK5; SLIT and NTRK like family member 5 [KO:K25836]\n 26285 CLDN17; claudin 17 [KO:K06087]\n 2734 GLG1; golgi glycoprotein 1 [KO:K06816]\n 29126 CD274; CD274 molecule [KO:K06745]\n 29851 ICOS; inducible T cell costimulator [KO:K06713]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490]\n 3384 ICAM2; intercellular adhesion molecule 2 [KO:K06523]\n 3385 ICAM3; intercellular adhesion molecule 3 [KO:K06486]\n 3655 ITGA6; integrin subunit alpha 6 [KO:K06485]\n 3676 ITGA4; integrin subunit alpha 4 [KO:K06483]\n 3680 ITGA9; integrin subunit alpha 9 [KO:K06585]\n 3683 ITGAL; integrin subunit alpha L [KO:K05718]\n 3684 ITGAM; integrin subunit alpha M [KO:K06461]\n 3685 ITGAV; integrin subunit alpha V [KO:K06487]\n 3688 ITGB1; integrin subunit beta 1 [KO:K05719]\n 3689 ITGB2; integrin subunit beta 2 [KO:K06464]\n 3695 ITGB7; integrin subunit beta 7 [KO:K06590]\n 3696 ITGB8; integrin subunit beta 8 [KO:K06591]\n 3897 L1CAM; L1 cell adhesion molecule [KO:K06550]\n 4099 MAG; myelin associated glycoprotein [KO:K06771]\n 4267 CD99; CD99 molecule (Xg blood group) [KO:K06520]\n 4359 MPZ; myelin protein zero [KO:K06770]\n 4684 NCAM1; neural cell adhesion molecule 1 [KO:K06491]\n 4685 NCAM2; neural cell adhesion molecule 2 [KO:K06491]\n 4756 NEO1; neogenin 1 [KO:K06766]\n 4897 NRCAM; neuronal cell adhesion molecule [KO:K06756]\n 49861 CLDN20; claudin 20 [KO:K06087]\n 5010 CLDN11; claudin 11 [KO:K06087]\n 50848 F11R; F11 receptor [KO:K06089]\n 51208 CLDN18; claudin 18 [KO:K06087]\n 5133 PDCD1; programmed cell death 1 [KO:K06744]\n 5175 PECAM1; platelet and endothelial cell adhesion molecule 1 [KO:K06471]\n 53842 CLDN22; claudin 22 [KO:K06087]\n 54413 NLGN3; neuroligin 3 [KO:K07378]\n 57502 NLGN4X; neuroligin 4 X-linked [KO:K07378]\n 57555 NLGN2; neuroligin 2 [KO:K07378]\n 57689 LRRC4C; leucine rich repeat containing 4C [KO:K07523]\n 57863 CADM3; cell adhesion molecule 3 [KO:K06780]\n 5788 PTPRC; protein tyrosine phosphatase receptor type C [KO:K06478] [EC:3.1.3.48]\n 5789 PTPRD; protein tyrosine phosphatase receptor type D [KO:K06777] [EC:3.1.3.48]\n 5792 PTPRF; protein tyrosine phosphatase receptor type F [KO:K05695] [EC:3.1.3.48]\n 5797 PTPRM; protein tyrosine phosphatase receptor type M [KO:K05693] [EC:3.1.3.48]\n 5802 PTPRS; protein tyrosine phosphatase receptor type S [KO:K06778] [EC:3.1.3.48]\n 5817 PVR; PVR cell adhesion molecule [KO:K06539]\n 5818 NECTIN1; nectin cell adhesion molecule 1 [KO:K06081]\n 5819 NECTIN2; nectin cell adhesion molecule 2 [KO:K06531]\n 58494 JAM2; junctional adhesion molecule 2 [KO:K06735]\n 6382 SDC1; syndecan 1 [KO:K06257]\n 6383 SDC2; syndecan 2 [KO:K16336]\n 6385 SDC4; syndecan 4 [KO:K16338]\n 6401 SELE; selectin E [KO:K06494]\n 6402 SELL; selectin L [KO:K06495]\n 6403 SELP; selectin P [KO:K06496]\n 6404 SELPLG; selectin P ligand [KO:K06544]\n 64101 LRRC4; leucine rich repeat containing 4 [KO:K16351]\n 64115 VSIR; V-set immunoregulatory receptor [KO:K23268]\n 644672 CLDN25; claudin 25 [KO:K06087]\n 6614 SIGLEC1; sialic acid binding Ig like lectin 1 [KO:K06548]\n 6693 SPN; sialophorin [KO:K06477]\n 6900 CNTN2; contactin 2 [KO:K06760]\n 7122 CLDN5; claudin 5 [KO:K06087]\n 7412 VCAM1; vascular cell adhesion molecule 1 [KO:K06527]\n 79679 VTCN1; V-set domain containing T cell activation inhibitor 1 [KO:K06747]\n 80380 PDCD1LG2; programmed cell death 1 ligand 2 [KO:K06708]\n 80381 CD276; CD276 molecule [KO:K06746]\n 8174 MADCAM1; mucosal vascular addressin cell adhesion molecule 1 [KO:K06779]\n 83692 CD99L2; CD99 molecule like 2 [KO:K06520]\n 83700 JAM3; junctional adhesion molecule 3 [KO:K06785]\n 84189 SLITRK6; SLIT and NTRK like family member 6 [KO:K25837]\n 84628 NTNG2; netrin G2 [KO:K16359]\n 84631 SLITRK2; SLIT and NTRK like family member 2 [KO:K25833]\n 8506 CNTNAP1; contactin associated protein 1 [KO:K07379]\n 8516 ITGA8; integrin subunit alpha 8 [KO:K06584]\n 9069 CLDN12; claudin 12 [KO:K06087]\n 9071 CLDN10; claudin 10 [KO:K06087]\n 9073 CLDN8; claudin 8 [KO:K06087]\n 9074 CLDN6; claudin 6 [KO:K06087]\n 9075 CLDN2; claudin 2 [KO:K06087]\n 9076 CLDN1; claudin 1 [KO:K06087]\n 9080 CLDN9; claudin 9 [KO:K06087]\n 90952 ESAM; endothelial cell adhesion molecule [KO:K06787]\n 914 CD2; CD2 molecule [KO:K06449]\n 920 CD4; CD4 molecule [KO:K06454]\n 923 CD6; CD6 molecule [KO:K06456]\n 925 CD8A; CD8 subunit alpha [KO:K06458]\n 926 CD8B; CD8 subunit beta [KO:K06459]\n 927 CD8B2; CD8B family member 2 [KO:K06459]\n 933 CD22; CD22 molecule [KO:K06467]\n 9369 NRXN3; neurexin 3 [KO:K07377]\n 9378 NRXN1; neurexin 1 [KO:K07377]\n 9379 NRXN2; neurexin 2 [KO:K07377]\n 940 CD28; CD28 molecule [KO:K06470]\n 94030 LRRC4B; leucine rich repeat containing 4B [KO:K16360]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 947 CD34; CD34 molecule [KO:K06474]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\n 965 CD58; CD58 molecule [KO:K06492]\n 9672 SDC3; syndecan 3 [KO:K16337]\n 999 CDH1; cadherin 1 [KO:K05689]\nREFERENCE PMID:14690046\n AUTHORS Barclay AN.\n TITLE Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules.\n JOURNAL Semin Immunol 15:215-23 (2003)\n DOI:10.1016/S1044-5323(03)00047-2\nREFERENCE PMID:11910893\n AUTHORS Sharpe AH, Freeman GJ.\n TITLE The B7-CD28 superfamily.\n JOURNAL Nat Rev Immunol 2:116-26 (2002)\n DOI:10.1038/nri727\nREFERENCE PMID:9597126\n AUTHORS Grewal IS, Flavell RA.\n TITLE CD40 and CD154 in cell-mediated immunity.\n JOURNAL Annu Rev Immunol 16:111-35 (1998)\n DOI:10.1146/annurev.immunol.16.1.111\nREFERENCE PMID:16034094\n AUTHORS Dardalhon V, Schubart AS, Reddy J, Meyers JH, Monney L, Sabatos CA, Ahuja R, Nguyen K, Freeman GJ, Greenfield EA, Sobel RA, Kuchroo VK.\n TITLE CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions.\n JOURNAL J Immunol 175:1558-65 (2005)\n DOI:10.4049/jimmunol.175.3.1558\nREFERENCE PMID:12234363\n AUTHORS Montoya MC, Sancho D, Vicente-Manzanares M, Sanchez-Madrid F.\n TITLE Cell adhesion and polarity during immune interactions.\n JOURNAL Immunol Rev 186:68-82 (2002)\n DOI:10.1034/j.1600-065X.2002.18607.x\nREFERENCE PMID:15071551\n AUTHORS Dejana E.\n TITLE Endothelial cell-cell junctions: happy together.\n JOURNAL Nat Rev Mol Cell Biol 5:261-70 (2004)\n DOI:10.1038/nrm1357\nREFERENCE PMID:14519386\n AUTHORS Bazzoni G.\n TITLE The JAM family of junctional adhesion molecules.\n JOURNAL Curr Opin Cell Biol 15:525-30 (2003)\n DOI:10.1016/S0955-0674(03)00104-2\nREFERENCE PMID:10798271\n AUTHORS Becker BF, Heindl B, Kupatt C, Zahler S.\n TITLE Endothelial function and hemostasis.\n JOURNAL Z Kardiol 89:160-7 (2000)\n DOI:10.1007/PL00007320\nREFERENCE PMID:9150551\n AUTHORS Elangbam CS, Qualls CW Jr, Dahlgren RR.\n TITLE Cell adhesion molecules--update.\n JOURNAL Vet Pathol 34:61-73 (1997)\n DOI:10.1177/030098589703400113\nREFERENCE PMID:12810109\n AUTHORS Muller WA.\n TITLE Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response.\n JOURNAL Trends Immunol 24:327-34 (2003)\n DOI:10.1016/S1471-4906(03)00117-0\nREFERENCE PMID:14519398\n AUTHORS Yamagata M, Sanes JR, Weiner JA.\n TITLE Synaptic adhesion molecules.\n JOURNAL Curr Opin Cell Biol 15:621-32 (2003)\n DOI:10.1016/S0955-0674(03)00107-8\nREFERENCE PMID:15882774\n AUTHORS Ethell IM, Pasquale EB.\n TITLE Molecular mechanisms of dendritic spine development and remodeling.\n JOURNAL Prog Neurobiol 75:161-205 (2005)\n DOI:10.1016/j.pneurobio.2005.02.003\nREFERENCE PMID:11050419\n AUTHORS Benson DL, Schnapp LM, Shapiro L, Huntley GW.\n TITLE Making memories stick: cell-adhesion molecules in synaptic plasticity.\n JOURNAL Trends Cell Biol 10:473-82 (2000)\n DOI:10.1016/S0962-8924(00)01838-9\nREFERENCE PMID:11860281\n AUTHORS Rosdahl JA, Mourton TL, Brady-Kalnay SM.\n TITLE Protein kinase C delta (PKCdelta) is required for protein tyrosine phosphatase mu (PTPmu)-dependent neurite outgrowth.\n JOURNAL Mol Cell Neurosci 19:292-306 (2002)\n DOI:10.1006/mcne.2001.1071\nREFERENCE PMID:10964748\n AUTHORS Dunican DJ, Doherty P.\n TITLE The generation of localized calcium rises mediated by cell adhesion molecules and their role in neuronal growth cone motility.\n JOURNAL Mol Cell Biol Res Commun 3:255-63 (2000)\n DOI:10.1006/mcbr.2000.0225\nREFERENCE PMID:12367625\n AUTHORS Girault JA, Peles E.\n TITLE Development of nodes of Ranvier.\n JOURNAL Curr Opin Neurobiol 12:476-85 (2002)\n DOI:10.1016/S0959-4388(02)00370-7\nREFERENCE PMID:10664064\n AUTHORS Arroyo EJ, Scherer SS.\n TITLE On the molecular architecture of myelinated fibers.\n JOURNAL Histochem Cell Biol 113:1-18 (2000)\n DOI:10.1007/s004180050001\nREFERENCE PMID:14556710\n AUTHORS Salzer JL.\n TITLE Polarized domains of myelinated axons.\n JOURNAL Neuron 40:297-318 (2003)\n DOI:10.1016/S0896-6273(03)00628-7\nREFERENCE PMID:15561584\n AUTHORS Irie K, Shimizu K, Sakisaka T, Ikeda W, Takai Y.\n TITLE Roles and modes of action of nectins in cell-cell adhesion.\n JOURNAL Semin Cell Dev Biol 15:643-56 (2004)\n DOI:10.1016/j.semcdb.2004.09.002\nREFERENCE PMID:15551862\n AUTHORS Nakanishi H, Takai Y.\n TITLE Roles of nectins in cell adhesion, migration and polarization.\n JOURNAL Biol Chem 385:885-92 (2004)\n DOI:10.1515/BC.2004.116\nREFERENCE PMID:15115723\n AUTHORS Siu MK, Cheng CY.\n TITLE Extracellular matrix: recent advances on its role in junction dynamics in the seminiferous epithelium during spermatogenesis.\n JOURNAL Biol Reprod 71:375-91 (2004)\n DOI:10.1095/biolreprod.104.028225\nREFERENCE PMID:15056568\n AUTHORS Lee NP, Cheng CY.\n TITLE Adaptors, junction dynamics, and spermatogenesis.\n JOURNAL Biol Reprod 71:392-404 (2004)\n DOI:10.1095/biolreprod.104.027268\nREFERENCE PMID:15728677\n AUTHORS Inagaki M, Irie K, Ishizaki H, Tanaka-Okamoto M, Morimoto K, Inoue E, Ohtsuka T, Miyoshi J, Takai Y.\n TITLE Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development.\n JOURNAL Development 132:1525-37 (2005)\n DOI:10.1242/dev.01697\nREFERENCE PMID:12500939\n AUTHORS Marthiens V, Gavard J, Lambert M, Mege RM.\n TITLE Cadherin-based cell adhesion in neuromuscular development.\n JOURNAL Biol Cell 94:315-26 (2002)\n DOI:10.1016/S0248-4900(02)00005-9\nREFERENCE PMID:15923648\n AUTHORS Krauss RS, Cole F, Gaio U, Takaesu G, Zhang W, Kang JS.\n TITLE Close encounters: regulation of vertebrate skeletal myogenesis by cell-cell contact.\n JOURNAL J Cell Sci 118:2355-62 (2005)\n DOI:10.1242/jcs.02397\nREL_PATHWAY hsa04520 Adherens junction\n hsa04530 Tight junction\n hsa04610 Complement and coagulation cascades\n hsa04660 T cell receptor signaling pathway\n hsa04670 Leukocyte transendothelial migration\nKO_PATHWAY ko04514\n///\n\nENTRY hsa04620 Pathway\nNAME Toll-like receptor signaling pathway - Homo sapiens (human)\nDESCRIPTION Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK.\nCLASS Organismal Systems; Immune system\nPATHWAY_MAP hsa04620 Toll-like receptor signaling pathway\nNETWORK nt06161 Human immunodeficiency virus 1 (HIV-1)\n nt06162 Hepatitis B virus (HBV)\n nt06163 Hepatitis C virus (HCV)\n nt06164 Kaposi sarcoma-associated herpesvirus (KSHV)\n nt06165 Epstein-Barr virus (EBV)\n nt06166 Human papillomavirus (HPV)\n nt06168 Herpes simplex virus 1 (HSV-1)\n nt06169 Measles virus (MV)\n nt06170 Influenza A virus (IAV)\n nt06171 SARS coronavirus 2 (SARS-CoV-2)\n nt06180 Pathogenic Escherichia coli\n nt06182 Shigella\n nt06183 Yersinia\n nt06222 IFN signaling (cancer)\n nt06263 Hepatocellular carcinoma\n nt06517 TLR signaling\n ELEMENT N00148 TLR3-IRF7 signaling pathway\n N00149 TLR3-IRF3 signaling pathway\n N00150 Type I IFN signaling pathway\n N00435 TLR1/2/4-NFKB signaling pathway\n N00438 TLR2/4-MAPK signaling pathway\n N00553 TLR4-IRF3/7 signaling pathway\n N00563 TLR3-NFKB signaling pathway\n N00690 TLR7/9-IRF7 signaling pathway\n N01543 TLR7/8/9-IRF5 signaling pathway\n N01566 TLR5-NFKB signaling pathway\nDRUG D00745 Interferon alfa-2a (USAN/INN)\n D00746 Interferon beta-1b (USAN/INN)\n D01666 Bropirimine (JAN/USAN/INN)\n D02500 Imiquimod (JAN/USP/INN)\n D02744 Interferon alfacon-1 (USAN/INN)\n D02745 Interferon alfa-2b (USAN)\n D02747 Peginterferon alfa-2a (USAN/INN)\n D02748 Peginterferon alfa-2b (USAN/INN)\n D03304 Interferon beta (JAN)\n D03305 Interferon alfa (NAMALWA) (JP18)\n D03441 Certolizumab pegol (USAN/INN)\n D04043 Eritoran tetrasodium (USAN)\n D04295 Galiximab (USAN/INN)\n D04552 Interferon alfa-n1 (USAN)\n D04553 Interferon alfa-n3 (USAN)\n D04554 Interferon beta-1a (USAN)\n D04619 Isatoribine (USAN)\n D04787 Loxoribine (USAN/INN)\n D06071 Teneliximab (USAN/INN)\n D06619 Mifamurtide (USAN)\n D06634 Relacatib (USAN/INN)\n D06635 Rilonacept (USAN/INN)\n D08841 Agatolimod (USAN)\n D08842 Agatolimod sodium (USAN)\n D08844 Albinterferon alfa-2b (USAN)\n D08955 Odanacatib (JAN/USAN)\n D09573 Eritoran sodium (JAN)\n D09639 Losmapimod (USAN/INN)\n D09661 Rintatolimod (USAN/INN)\n D10483 Peginterferon beta-1a (USAN/INN)\n D11003 Vesatolimod (USAN/INN)\n D11027 Ropeginterferon alfa-2b (INN)\n D11357 Bleselumab (USAN/INN)\n D11491 Selicrelumab (USAN/INN)\n D11503 Tomaralimab (USAN)\n D11504 Tilsotolimod (USAN/INN)\n D11505 Tilsotolimod sodium (USAN)\n D11597 Ravagalimab (USAN/INN)\n D11610 Iscalimab (USAN/INN)\n D11668 Mosedipimod (USAN/INN)\n D11871 Selgantolimod (USAN/INN)\n D12167 Zimlovisertib (USAN)\n D12178 Sotigalimab (USAN)\n D12261 Enpatoran (USAN/INN)\n D12275 Cobitolimod (USAN/INN)\n D12276 Cobitolimod sodium (USAN)\n D12352 Eclitasertib (USAN/INN)\n D12411 Emavusertib (USAN/INN)\n D12412 Emavusertib hydrochloride (USAN)\n D12453 Guretolimod (USAN/INN)\n D12463 Davoceticept (USAN/INN)\n D12464 Dazukibart (USAN)\n D12521 Ruzotolimod (USAN/INN)\n D12532 Emavusertib mesylate (USAN)\n D12533 Emavusertib maleate (USAN)\n D12538 Emavusertib phosphate (USAN)\n D12539 emavusertib tosylate (USAN)\n D12624 Paridiprubart (USAN/INN)\n D12725 Lomedeucitinib (USAN)\n D12821 Flizasertib (USAN/INN)\n D12846 Ocadusertib (USAN)\n D12855 Nelitolimod (USAN)\n D12856 Nelitolimod sodium (USAN)\n D12929 Vamikibart (USAN/INN)\n D12936 Vidutolimod (USAN/INN)\n D12940 Oditrasertib (USAN/INN)\n D12941 Zasocitinib (USAN/INN)\n D13033 Abiprubart (USAN/INN)\n D13049 Pacibekitug (USAN/INN)\n D13051 Resiquimod sulfate (USAN)\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 10000 AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]\n 10333 TLR6; toll like receptor 6 [KO:K10169]\n 10379 IRF9; interferon regulatory factor 9 [KO:K04693]\n 10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]\n 110117499 P3R3URF-PIK3R3; P3R3URF-PIK3R3 readthrough [KO:K02649]\n 114609 TIRAP; TIR domain containing adaptor protein [KO:K05403]\n 1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]\n 1326 MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]\n 1432 MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]\n 148022 TICAM1; TIR domain containing adaptor molecule 1 [KO:K05842]\n 1513 CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]\n 207 AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]\n 208 AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]\n 23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404]\n 2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]\n 23643 LY96; lymphocyte antigen 96 [KO:K05400]\n 29110 TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]\n 3439 IFNA1; interferon alpha 1 [KO:K05414]\n 3440 IFNA2; interferon alpha 2 [KO:K05414]\n 3441 IFNA4; interferon alpha 4 [KO:K05414]\n 3442 IFNA5; interferon alpha 5 [KO:K05414]\n 3443 IFNA6; interferon alpha 6 [KO:K05414]\n 3444 IFNA7; interferon alpha 7 [KO:K05414]\n 3445 IFNA8; interferon alpha 8 [KO:K05414]\n 3446 IFNA10; interferon alpha 10 [KO:K05414]\n 3447 IFNA13; interferon alpha 13 [KO:K05414]\n 3448 IFNA14; interferon alpha 14 [KO:K05414]\n 3449 IFNA16; interferon alpha 16 [KO:K05414]\n 3451 IFNA17; interferon alpha 17 [KO:K05414]\n 3452 IFNA21; interferon alpha 21 [KO:K05414]\n 3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]\n 3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]\n 3456 IFNB1; interferon beta 1 [KO:K05415]\n 353376 TICAM2; TIR domain containing adaptor molecule 2 [KO:K05409]\n 3551 IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]\n 3553 IL1B; interleukin 1 beta [KO:K04519]\n 3569 IL6; interleukin 6 [KO:K05405]\n 3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]\n 3592 IL12A; interleukin 12A [KO:K05406]\n 3593 IL12B; interleukin 12B [KO:K05425]\n 3627 CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]\n 3654 IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]\n 3661 IRF3; interferon regulatory factor 3 [KO:K05411]\n 3663 IRF5; interferon regulatory factor 5 [KO:K09446]\n 3665 IRF7; interferon regulatory factor 7 [KO:K09447]\n 3716 JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]\n 3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]\n 388372 CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964]\n 3929 LBP; lipopolysaccharide binding protein [KO:K05399]\n 414062 CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]\n 4283 CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]\n 4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729]\n 4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]\n 4792 NFKBIA; NFKB inhibitor alpha [KO:K04734]\n 51135 IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]\n 51284 TLR7; toll like receptor 7 [KO:K05404]\n 51311 TLR8; toll like receptor 8 [KO:K10170]\n 5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]\n 5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]\n 5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]\n 5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]\n 5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]\n 54106 TLR9; toll like receptor 9 [KO:K10161]\n 54472 TOLLIP; toll interacting protein [KO:K05402]\n 5594 MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]\n 5595 MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]\n 5599 MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]\n 5600 MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]\n 5601 MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]\n 5602 MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]\n 5603 MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]\n 5604 MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]\n 5605 MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]\n 5606 MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]\n 5608 MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]\n 5609 MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]\n 5879 RAC1; Rac family small GTPase 1 [KO:K04392]\n 5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]\n 6300 MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]\n 6348 CCL3; C-C motif chemokine ligand 3 [KO:K05408]\n 6349 CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]\n 6351 CCL4; C-C motif chemokine ligand 4 [KO:K12964]\n 6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499]\n 6373 CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]\n 6416 MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]\n 6696 SPP1; secreted phosphoprotein 1 [KO:K06250]\n 6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220]\n 6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221]\n 6885 MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]\n 7096 TLR1; toll like receptor 1 [KO:K05398]\n 7097 TLR2; toll like receptor 2 [KO:K10159]\n 7098 TLR3; toll like receptor 3 [KO:K05401]\n 7099 TLR4; toll like receptor 4 [KO:K10160]\n 7100 TLR5; toll like receptor 5 [KO:K10168]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 7187 TRAF3; TNF receptor associated factor 3 [KO:K03174]\n 7189 TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]\n 7297 TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]\n 841 CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]\n 8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]\n 8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]\n 8737 RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]\n 8772 FADD; Fas associated via death domain [KO:K02373]\n 929 CD14; CD14 molecule [KO:K04391]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 9560 CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964]\n 958 CD40; CD40 molecule [KO:K03160]\n 9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]\nREFERENCE PMID:17275323\n AUTHORS Kawai T, Akira S.\n TITLE TLR signaling.\n JOURNAL Semin Immunol 19:24-32 (2007)\n DOI:10.1016/j.smim.2006.12.004\nREFERENCE PMID:17457343\n AUTHORS O'Neill LA, Bowie AG.\n TITLE The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.\n JOURNAL Nat Rev Immunol 7:353-64 (2007)\n DOI:10.1038/nri2079\nREFERENCE PMID:16932750\n AUTHORS Honda K, Taniguchi T.\n TITLE IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.\n JOURNAL Nat Rev Immunol 6:644-58 (2006)\n DOI:10.1038/nri1900\nREFERENCE PMID:17395581\n AUTHORS Uematsu S, Akira S.\n TITLE Toll-like receptors and Type I interferons.\n JOURNAL J Biol Chem 282:15319-23 (2007)\n DOI:10.1074/jbc.R700009200\nREFERENCE PMID:16497588\n AUTHORS Akira S, Uematsu S, Takeuchi O.\n TITLE Pathogen recognition and innate immunity.\n JOURNAL Cell 124:783-801 (2006)\n DOI:10.1016/j.cell.2006.02.015\nREFERENCE PMID:14698224\n AUTHORS Yamamoto M, Takeda K, Akira S.\n TITLE TIR domain-containing adaptors define the specificity of TLR signaling.\n JOURNAL Mol Immunol 40:861-8 (2004)\n DOI:10.1016/j.molimm.2003.10.006\nREFERENCE PMID:12734364\n AUTHORS Means TK, Hayashi F, Smith KD, Aderem A, Luster AD.\n TITLE The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells.\n JOURNAL J Immunol 170:5165-75 (2003)\n DOI:10.4049/jimmunol.170.10.5165\nREFERENCE PMID:14751764\n AUTHORS Aderem A, Smith KD.\n TITLE A systems approach to dissecting immunity and inflammation.\n JOURNAL Semin Immunol 16:55-67 (2004)\n DOI:10.1016/j.smim.2003.10.002\nREFERENCE PMID:17637696\n AUTHORS Banerjee A, Gerondakis S.\n TITLE Coordinating TLR-activated signaling pathways in cells of the immune system.\n JOURNAL Immunol Cell Biol 85:420-4 (2007)\n DOI:10.1038/sj.icb.7100098\nREFERENCE PMID:17507094\n AUTHORS Loniewski KJ, Patial S, Parameswaran N.\n TITLE Sensitivity of TLR4- and -7-induced NF kappa B1 p105-TPL2-ERK pathway to TNF-receptor-associated-factor-6 revealed by RNAi in mouse macrophages.\n JOURNAL Mol Immunol 44:3715-23 (2007)\n DOI:10.1016/j.molimm.2007.04.002\nREFERENCE PMID:11101877\n AUTHORS Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG.\n TITLE Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.\n JOURNAL Nat Immunol 1:533-40 (2000)\n DOI:10.1038/82797\nREFERENCE PMID:16924467\n AUTHORS Uematsu S, Akira S.\n TITLE Toll-like receptors and innate immunity.\n JOURNAL J Mol Med 84:712-25 (2006)\n DOI:10.1007/s00109-006-0084-y\nREL_PATHWAY hsa04010 MAPK signaling pathway\n hsa04060 Cytokine-cytokine receptor interaction\n hsa04064 NF-kappa B signaling pathway\n hsa04120 Ubiquitin mediated proteolysis\n hsa04151 PI3K-Akt signaling pathway\n hsa04210 Apoptosis\n hsa04610 Complement and coagulation cascades\n hsa04630 JAK-STAT signaling pathway\nKO_PATHWAY ko04620\n///\n\nENTRY hsa04672 Pathway\nNAME Intestinal immune network for IgA production - Homo sapiens (human)\nDESCRIPTION The intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies that serve as the first line of defense against microorganisms. The basic map of IgA production includes induction of mucosal B cells in the Peyer's patches, circulation through the bloodstream and homing to intestinal mucosa of IgA-commited plasma cells, and local antibody production for export across the intestinal membranes. Multiple cytokines, including TGF-{beta}, IL-10, IL-4, IL-5, and IL-6, are required to promote IgA class switching and terminal differentiation process of the B cells. Secreted IgA promotes immune exclusion by entrapping dietary antigens and microorganisms in the mucus and functions for neutralization of toxins and pathogenic microbes.\nCLASS Organismal Systems; Immune system\nPATHWAY_MAP hsa04672 Intestinal immune network for IgA production\nDRUG D03203 Abatacept (USAN/INN)\n D03222 Belatacept (USAN/INN)\n D09799 Carotegrast methyl (JAN)\n D09901 Etrolizumab (USAN/INN)\n D10028 Valategrast hydrochloride (USAN)\n D10378 Vercirnon (USAN/INN)\n D10379 Vercirnon sodium (USAN)\n D11281 Reltecimod (USAN/INN)\n D11348 Reltecimod sodium (USAN)\n D11556 Idecabtagene vicleucel (USAN)\n D11594 Belantamab (USAN/INN)\n D11595 Belantamab mafodotin (USAN)\n D11821 Nogapendekin alfa (USAN/INN)\n D11907 Rozibafusp alfa (USAN/INN)\n D11992 Pavurutamab (USAN)\n D11996 Feladilimab (USAN/INN)\n D12010 Pacanalotamab (USAN)\n D12151 Ianalumab (USAN/INN)\n D12195 Izuralimab (USAN)\n D12222 Linvoseltamab (USAN)\n D12300 Acazicolcept (USAN/INN)\n D12306 Ordesekimab (USAN)\n D12315 Ciltacabtagene autoleucel (USAN/INN)\n D12374 Sibeprenlimab (INN)\n D12620 Frexalimab (USAN/INN)\n D12623 Nanrilkefusp alfa (USAN/INN)\n D12800 Zigakibart (USAN/INN)\n D12803 Povetacicept (USAN/INN)\n D12888 Nogapendekin alfa inbakicept\n D12913 Ingitamig (USAN)\n D12990 Etentamig (USAN/INN)\n D13033 Abiprubart (USAN/INN)\nDBLINKS GO: 0002387\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 102723996 [KO:K06710]\n 10673 TNFSF13B; TNF superfamily member 13b [KO:K05476]\n 10803 CCR9; C-C motif chemokine receptor 9 [KO:K04184]\n 115650 TNFRSF13C; TNF receptor superfamily member 13C [KO:K05151]\n 23308 ICOSLG; inducible T cell costimulator ligand [KO:K06710]\n 23495 TNFRSF13B; TNF receptor superfamily member 13B [KO:K05150]\n 2826 CCR10; C-C motif chemokine receptor 10 [KO:K04185]\n 29851 ICOS; inducible T cell costimulator [KO:K06713]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3558 IL2; interleukin 2 [KO:K05429]\n 3565 IL4; interleukin 4 [KO:K05430]\n 3567 IL5; interleukin 5 [KO:K05428]\n 3569 IL6; interleukin 6 [KO:K05405]\n 3586 IL10; interleukin 10 [KO:K05443]\n 3600 IL15; interleukin 15 [KO:K05433]\n 3601 IL15RA; interleukin 15 receptor subunit alpha [KO:K05074]\n 3676 ITGA4; integrin subunit alpha 4 [KO:K06483]\n 3695 ITGB7; integrin subunit beta 7 [KO:K06590]\n 4055 LTBR; lymphotoxin beta receptor [KO:K03159]\n 5284 PIGR; polymeric immunoglobulin receptor [KO:K13073]\n 56477 CCL28; C-C motif chemokine ligand 28 [KO:K05513]\n 57379 AICDA; activation induced cytidine deaminase [KO:K10989] [EC:3.5.4.38]\n 608 TNFRSF17; TNF receptor superfamily member 17 [KO:K05153]\n 6370 CCL25; C-C motif chemokine ligand 25 [KO:K13072]\n 6387 CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]\n 7040 TGFB1; transforming growth factor beta 1 [KO:K13375]\n 7852 CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]\n 8174 MADCAM1; mucosal vascular addressin cell adhesion molecule 1 [KO:K06779]\n 8741 TNFSF13; TNF superfamily member 13 [KO:K05475]\n 9020 MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\nCOMPOUND C00777 Retinoate\n C15493 9-cis-Retinoic acid\nREFERENCE PMID:12511876\n AUTHORS Fagarasan S, Honjo T\n TITLE Intestinal IgA synthesis: regulation of front-line body defences.\n JOURNAL Nat Rev Immunol 3:63-72 (2003)\n DOI:10.1038/nri982\nREFERENCE PMID:19079156\n AUTHORS Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P\n TITLE The immune geography of IgA induction and function.\n JOURNAL Mucosal Immunol 1:11-22 (2008)\n DOI:10.1038/mi.2007.6\nREFERENCE PMID:15971106\n AUTHORS Kunisawa J, Kiyono H\n TITLE A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense.\n JOURNAL Cell Mol Life Sci 62:1308-21 (2005)\n DOI:10.1007/s00018-005-5035-1\nREFERENCE PMID:18549797\n AUTHORS Cerutti A, Rescigno M\n TITLE The biology of intestinal immunoglobulin A responses.\n JOURNAL Immunity 28:740-50 (2008)\n DOI:10.1016/j.immuni.2008.05.001\nREFERENCE PMID:18243016\n AUTHORS Tsuji M, Suzuki K, Kinoshita K, Fagarasan S\n TITLE Dynamic interactions between bacteria and immune cells leading to intestinal IgA synthesis.\n JOURNAL Semin Immunol 20:59-66 (2008)\n DOI:10.1016/j.smim.2007.12.003\nREFERENCE PMID:17182536\n AUTHORS Corthesy B\n TITLE Roundtrip ticket for secretory IgA: role in mucosal homeostasis?\n JOURNAL J Immunol 178:27-32 (2007)\n DOI:10.4049/jimmunol.178.1.27\nREFERENCE PMID:18838301\n AUTHORS Suzuki K, Fagarasan S\n TITLE How host-bacterial interactions lead to IgA synthesis in the gut.\n JOURNAL Trends Immunol 29:523-31 (2008)\n DOI:10.1016/j.it.2008.08.001\nREFERENCE PMID:19079167\n AUTHORS Mora JR, von Andrian UH\n TITLE Differentiation and homing of IgA-secreting cells.\n JOURNAL Mucosal Immunol 1:96-109 (2008)\n DOI:10.1038/mi.2007.14\nREFERENCE PMID:17161619\n AUTHORS Suzuki K, Ha SA, Tsuji M, Fagarasan S\n TITLE Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut.\n JOURNAL Semin Immunol 19:127-35 (2007)\n DOI:10.1016/j.smim.2006.10.001\nREFERENCE PMID:18483500\n AUTHORS Cerutti A\n TITLE The regulation of IgA class switching.\n JOURNAL Nat Rev Immunol 8:421-34 (2008)\n DOI:10.1038/nri2322\nREL_PATHWAY hsa04612 Antigen processing and presentation\n hsa04660 T cell receptor signaling pathway\n hsa04662 B cell receptor signaling pathway\n hsa04670 Leukocyte transendothelial migration\nKO_PATHWAY ko04672\n///\n\nENTRY hsa04940 Pathway\nNAME Type I diabetes mellitus - Homo sapiens (human)\nDESCRIPTION Type I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-presenting cell (APC), such as macrophages and dendritic cells, and presented in a complex with MHC-II molecules on the surface of the APC. Then immunogenic signals from APC activate CD4+ T cells, predominantly of the Th1 subset. Antigen-activated Th1 cells produce IL-2 and IFNgamma. They activate macrophages and cytotoxic CD8+ T cells, and these effector cells may kill islet beta-cells by one or both of two types of mechanisms: (1) direct interactions of antigen-specific cytotoxic T cells with a beta-cell autoantigen-MHC-I complex on the beta-cell, and (2) non-specific inflammatory mediators, such as free radicals/oxidants and cytokines (IL-1, TNFalpha, TNFbeta, IFNgamma).\n Type I diabetes is a polygenic disease. One of the principle determining genetic factors in diabetes incidence is the inheritance of mutant MHC-II alleles. Another plausible candidate gene is the insulin gene.\nCLASS Human Diseases; Endocrine and metabolic disease\nPATHWAY_MAP hsa04940 Type I diabetes mellitus\nDISEASE H00408 Type 1 diabetes mellitus\nDRUG D04748 Lisofylline (USAN/INN)\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 1363 CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]\n 2571 GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]\n 2572 GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]\n 3002 GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3329 HSPD1; heat shock protein family D (Hsp60) member 1 [KO:K04077] [EC:5.6.1.7]\n 3382 ICA1; islet cell autoantigen 1 [KO:K19863]\n 3458 IFNG; interferon gamma [KO:K04687]\n 355 FAS; Fas cell surface death receptor [KO:K04390]\n 3552 IL1A; interleukin 1 alpha [KO:K04383]\n 3553 IL1B; interleukin 1 beta [KO:K04519]\n 3558 IL2; interleukin 2 [KO:K05429]\n 356 FASLG; Fas ligand [KO:K04389]\n 3592 IL12A; interleukin 12A [KO:K05406]\n 3593 IL12B; interleukin 12B [KO:K05425]\n 3630 INS; insulin [KO:K04526]\n 4049 LTA; lymphotoxin alpha [KO:K05468]\n 5551 PRF1; perforin 1 [KO:K07818]\n 5798 PTPRN; protein tyrosine phosphatase receptor type N [KO:K07817] [EC:3.1.3.48]\n 5799 PTPRN2; protein tyrosine phosphatase receptor type N2 [KO:K07817] [EC:3.1.3.48]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\nCOMPOUND C00027 Hydrogen peroxide\n C00533 Nitric oxide\n C00704 Superoxide\nREFERENCE PMID:9719467\n AUTHORS Rabinovitch A, Suarez-Pinzon WL.\n TITLE Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus.\n JOURNAL Biochem Pharmacol 55:1139-49 (1998)\n DOI:10.1016/S0006-2952(97)00492-9\nREFERENCE PMID:11507694\n AUTHORS Cox NJ, Wapelhorst B, Morrison VA, Johnson L, Pinchuk L, Spielman RS, Todd JA, Concannon P\n TITLE Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families.\n JOURNAL Am J Hum Genet 69:820-30 (2001)\n DOI:10.1086/323501\nREFERENCE PMID:8072542\n AUTHORS Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, Reed PW, Gough SC, Jenkins SC, Palmer SM, et al.\n TITLE A genome-wide search for human type 1 diabetes susceptibility genes.\n JOURNAL Nature 371:130-6 (1994)\n DOI:10.1038/371130a0\nREFERENCE PMID:8786033\n AUTHORS Fujisawa T, Ikegami H, Kawaguchi Y, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Ueda H, Shima K, Ogihara T.\n TITLE Class I HLA is associated with age-at-onset of IDDM, while class II HLA confers susceptibility to IDDM.\n JOURNAL Diabetologia 38:1493-5 (1995)\n DOI:10.1007/BF00400620\nREFERENCE PMID:12796471\n AUTHORS Jaeckel E, Klein L, Martin-Orozco N, von Boehmer H.\n TITLE Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.\n JOURNAL J Exp Med 197:1635-44 (2003)\n DOI:10.1084/jem.20030215\nREFERENCE PMID:15889095\n AUTHORS Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS.\n TITLE Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice.\n JOURNAL Nature 435:220-3 (2005)\n DOI:10.1038/nature03523\nREFERENCE PMID:15889096\n AUTHORS Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA.\n TITLE Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.\n JOURNAL Nature 435:224-8 (2005)\n DOI:10.1038/nature03625\nREFERENCE PMID:14617043\n AUTHORS Lieberman SM, DiLorenzo TP.\n TITLE A comprehensive guide to antibody and T-cell responses in type 1 diabetes.\n JOURNAL Tissue Antigens 62:359-77 (2003)\n DOI:10.1034/j.1399-0039.2003.00152.x\nREFERENCE PMID:12752668\n AUTHORS Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.\n TITLE Granzyme B: a natural born killer.\n JOURNAL Immunol Rev 193:31-8 (2003)\n DOI:10.1034/j.1600-065X.2003.00044.x\nREL_PATHWAY hsa04210 Apoptosis\n hsa04660 T cell receptor signaling pathway\nKO_PATHWAY ko04940\n///\n\nENTRY hsa05320 Pathway\nNAME Autoimmune thyroid disease - Homo sapiens (human)\nDESCRIPTION The classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroiditis or primary myxedema. HT is characterized by the presence of goitre, thyroid autoantibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg) in serum and varying degrees of thyroid dysfunction. During HT, self-reactive CD4+ T lymphocytes (Th) recruit B cells and CD8+ T cells (CTL) into the thyroid. Disease progression leads to the death of thyroid cells and hypothyroidism. Both autoantibodies and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion. In GD, the TSH-R is the most important autoantigen. Antibodies directed against it mimic the effects of the hormone on thyroid cells, TSH, stimulating autonomous production of thyroxine and triiodothyronine and causing hyperthyroidism. The presence of TSH-R-blocking antibodies that bind the TSH receptor in a similar fashion to the antibodies in patients with Grave's disease but that block rather than activate the receptor explains some cases of atrophic hypothyroidism.\nCLASS Human Diseases; Immune disease\nPATHWAY_MAP hsa05320 Autoimmune thyroid disease\nDRUG D00562 Propylthiouracil (JP18/USP/INN)\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 1081 CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]\n 1493 CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]\n 3002 GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3439 IFNA1; interferon alpha 1 [KO:K05414]\n 3440 IFNA2; interferon alpha 2 [KO:K05414]\n 3441 IFNA4; interferon alpha 4 [KO:K05414]\n 3442 IFNA5; interferon alpha 5 [KO:K05414]\n 3443 IFNA6; interferon alpha 6 [KO:K05414]\n 3444 IFNA7; interferon alpha 7 [KO:K05414]\n 3445 IFNA8; interferon alpha 8 [KO:K05414]\n 3446 IFNA10; interferon alpha 10 [KO:K05414]\n 3447 IFNA13; interferon alpha 13 [KO:K05414]\n 3448 IFNA14; interferon alpha 14 [KO:K05414]\n 3449 IFNA16; interferon alpha 16 [KO:K05414]\n 3451 IFNA17; interferon alpha 17 [KO:K05414]\n 3452 IFNA21; interferon alpha 21 [KO:K05414]\n 355 FAS; Fas cell surface death receptor [KO:K04390]\n 3558 IL2; interleukin 2 [KO:K05429]\n 356 FASLG; Fas ligand [KO:K04389]\n 3565 IL4; interleukin 4 [KO:K05430]\n 3567 IL5; interleukin 5 [KO:K05428]\n 3586 IL10; interleukin 10 [KO:K05443]\n 5551 PRF1; perforin 1 [KO:K07818]\n 7038 TG; thyroglobulin [KO:K10809]\n 7173 TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]\n 7252 TSHB; thyroid stimulating hormone subunit beta [KO:K05251]\n 7253 TSHR; thyroid stimulating hormone receptor [KO:K04249]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\nCOMPOUND C01382 Iodine\n C01829 Thyroxine\n C02465 Triiodothyronine\n D00636 Amiodarone hydrochloride (JP18/USP)\nREFERENCE PMID:15049952\n AUTHORS Fountoulakis S, Tsatsoulis A.\n TITLE On the pathogenesis of autoimmune thyroid disease: a unifying hypothesis.\n JOURNAL Clin Endocrinol (Oxf) 60:397-409 (2004)\n DOI:10.1046/j.1365-2265.2004.01978.x\nREFERENCE PMID:15762980\n AUTHORS Chistiakov DA.\n TITLE Immunogenetics of Hashimoto's thyroiditis.\n JOURNAL J Autoimmune Dis 2:1 (2005)\n DOI:10.1186/1740-2557-2-1\nREFERENCE PMID:9534029\n AUTHORS McIver B, Morris JC.\n TITLE The pathogenesis of Graves' disease.\n JOURNAL Endocrinol Metab Clin North Am 27:73-89 (1998)\n DOI:10.1016/S0889-8529(05)70299-1\nREFERENCE PMID:11913070\n AUTHORS Stassi G, De Maria R.\n TITLE Autoimmune thyroid disease: new models of cell death in autoimmunity.\n JOURNAL Nat Rev Immunol 2:195-204 (2002)\n DOI:10.1038/nri750\nREFERENCE PMID:12192541\n AUTHORS Collins J, Gough S.\n TITLE Autoimmunity in thyroid disease.\n JOURNAL Eur J Nucl Med Mol Imaging 29 Suppl 2:S417-24 (2002)\n DOI:10.1007/s00259-002-0848-8\nREFERENCE PMID:11396701\n AUTHORS Ruwhof C, Drexhage HA.\n TITLE Iodine and thyroid autoimmune disease in animal models.\n JOURNAL Thyroid 11:427-36 (2001)\n DOI:10.1089/105072501300176381\nREFERENCE PMID:17192582\n AUTHORS Tsatsoulis A.\n TITLE The role of stress in the clinical expression of thyroid autoimmunity.\n JOURNAL Ann N Y Acad Sci 1088:382-95 (2006)\n DOI:10.1196/annals.1366.015\nREFERENCE PMID:15132715\n AUTHORS Prummel MF, Strieder T, Wiersinga WM.\n TITLE The environment and autoimmune thyroid diseases.\n JOURNAL Eur J Endocrinol 150:605-18 (2004)\n DOI:10.1530/eje.0.1500605\nREFERENCE PMID:11577986\n AUTHORS Kopp P.\n TITLE The TSH receptor and its role in thyroid disease.\n JOURNAL Cell Mol Life Sci 58:1301-22 (2001)\n DOI:10.1007/PL00000941\nREL_PATHWAY hsa04210 Apoptosis\n hsa04514 Cell adhesion molecules\n hsa04610 Complement and coagulation cascades\n hsa04612 Antigen processing and presentation\n hsa04660 T cell receptor signaling pathway\n hsa04662 B cell receptor signaling pathway\n hsa04918 Thyroid hormone synthesis\nKO_PATHWAY ko05320\n///\n\nENTRY hsa05322 Pathway\nNAME Systemic lupus erythematosus - Homo sapiens (human)\nDESCRIPTION Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and certain cytoplasmic components, in association with a diverse array of clinical manifestations. The primary pathological findings in patients with SLE are those of inflammation, vasculitis, immune complex deposition, and vasculopathy. Immune complexes comprising autoantibody and self-antigen is deposited particulary in the renal glomeruli and mediate a systemic inflammatory response by activating complement or via Fc{gamma}R-mediated neutrophil and macrophage activation. Activation of complement (C5) leads to injury both through formation of the membrane attack complex (C5b-9) or by generation of the anaphylatoxin and cell activator C5a. Neutrophils and macrophages cause tissue injury by the release of oxidants and proteases.\nCLASS Human Diseases; Immune disease\nPATHWAY_MAP hsa05322 Systemic lupus erythematosus\nDISEASE H00080 Systemic lupus erythematosus\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 100293534 C4B_2; complement component 4B (Chido/Rodgers blood group), copy 2 [KO:K03989]\n 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 102724334 [KO:K11252]\n 110384692 [KO:K03989]\n 114483833 H2BK1; H2B.K variant histone 1 [KO:K11252]\n 115482686 H2AL3; H2A.L variant histone 3 [KO:K11251]\n 121504 H4C16; H4 histone 16 [KO:K11254]\n 124905743 FCGR3B; low affinity immunoglobulin gamma Fc region receptor III-B [KO:K06463]\n 126961 H3C14; H3 clustered histone 14 [KO:K11253]\n 128312 H2BC26; H2B clustered histone 26 [KO:K11252]\n 1511 CTSG; cathepsin G [KO:K01319] [EC:3.4.21.20]\n 158983 H2BW1; H2B.W histone 1 [KO:K11252]\n 1991 ELANE; elastase, neutrophil expressed [KO:K01327] [EC:3.4.21.37]\n 2209 FCGR1A; Fc gamma receptor Ia [KO:K06498]\n 2212 FCGR2A; Fc gamma receptor IIa [KO:K06472]\n 2214 FCGR3A; Fc gamma receptor IIIa [KO:K06463]\n 2215 FCGR3B; Fc gamma receptor IIIb [KO:K06463]\n 221613 H2AC1; H2A clustered histone 1 [KO:K11251]\n 255626 H2BC1; H2B clustered histone 1 [KO:K11252]\n 286436 H2BW2; H2B.W histone 2 [KO:K11252]\n 2903 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]\n 2904 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]\n 3012 H2AC8; H2A clustered histone 8 [KO:K11251]\n 3013 H2AC7; H2A clustered histone 7 [KO:K11251]\n 3014 H2AX; H2A.X variant histone [KO:K11251]\n 3015 H2AZ1; H2A.Z variant histone 1 [KO:K11251]\n 3017 H2BC5; H2B clustered histone 5 [KO:K11252]\n 3018 H2BC3; H2B clustered histone 3 [KO:K11252]\n 3020 H3-3A; H3.3 histone A [KO:K11253]\n 3021 H3-3B; H3.3 histone B [KO:K11253]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 317772 H2AC21; H2A clustered histone 21 [KO:K11251]\n 333932 H3C15; H3 clustered histone 15 [KO:K11253]\n 3458 IFNG; interferon gamma [KO:K04687]\n 3586 IL10; interleukin 10 [KO:K05443]\n 440093 H3-5; H3.5 histone [KO:K11253]\n 440689 H2BC18; H2B clustered histone 18 [KO:K11252]\n 474381 H2AB2; H2A.B variant histone 2 [KO:K11251]\n 474382 H2AB1; H2A.B variant histone 1 [KO:K11251]\n 54145 H2BC12L; H2B clustered histone 12 like [KO:K11252]\n 554313 H4C15; H4 clustered histone 15 [KO:K11254]\n 55506 MACROH2A2; macroH2A.2 histone [KO:K11251]\n 55766 H2AJ; H2A.J histone [KO:K11251]\n 653604 H3C13; H3 clustered histone 13 [KO:K11253]\n 6628 SNRPB; small nuclear ribonucleoprotein polypeptides B and B1 [KO:K11086]\n 6632 SNRPD1; small nuclear ribonucleoprotein D1 polypeptide [KO:K11087]\n 6634 SNRPD3; small nuclear ribonucleoprotein D3 polypeptide [KO:K11088]\n 6737 TRIM21; tripartite motif containing 21 [KO:K10651] [EC:2.3.2.27]\n 6738 RO60; Ro60, Y RNA binding protein [KO:K11089]\n 6741 SSB; small RNA binding exonuclease protection factor La [KO:K11090]\n 712 C1QA; complement C1q A chain [KO:K03986]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 713 C1QB; complement C1q B chain [KO:K03987]\n 714 C1QC; complement C1q C chain [KO:K03988]\n 715 C1R; complement C1r [KO:K01330] [EC:3.4.21.41]\n 716 C1S; complement C1s [KO:K01331] [EC:3.4.21.42]\n 717 C2; complement C2 [KO:K01332] [EC:3.4.21.43]\n 718 C3; complement C3 [KO:K03990]\n 720 C4A; complement C4A (Chido/Rodgers blood group) [KO:K03989]\n 721 C4B; complement C4B (Chido/Rodgers blood group) [KO:K03989]\n 723790 H2AC19; H2A clustered histone 19 [KO:K11251]\n 727 C5; complement C5 [KO:K03994]\n 729 C6; complement C6 [KO:K03995]\n 730 C7; complement C7 [KO:K03996]\n 731 C8A; complement C8 alpha chain [KO:K03997]\n 732 C8B; complement C8 beta chain [KO:K03998]\n 733 C8G; complement C8 gamma chain [KO:K03999]\n 735 C9; complement C9 [KO:K04000]\n 81 ACTN4; actinin alpha 4 [KO:K05699]\n 8290 H3-4; H3.4 histone, cluster member [KO:K11253]\n 8294 H4C9; H4 clustered histone 9 [KO:K11254]\n 8329 H2AC13; H2A clustered histone 13 [KO:K11251]\n 8330 H2AC15; H2A clustered histone 15 [KO:K11251]\n 8331 H2AC14; H2A clustered histone 14 [KO:K11251]\n 8332 H2AC16; H2A clustered histone 16 [KO:K11251]\n 8334 H2AC6; H2A clustered histone 6 [KO:K11251]\n 8335 H2AC4; H2A clustered histone 4 [KO:K11251]\n 8336 H2AC17; H2A clustered histone 17 [KO:K11251]\n 8337 H2AC18; H2A clustered histone 18 [KO:K11251]\n 8338 H2AC20; H2A clustered histone 20 [KO:K11251]\n 8339 H2BC8; H2B clustered histone 8 [KO:K11252]\n 8340 H2BC13; H2B clustered histone 13 [KO:K11252]\n 8341 H2BC15; H2B clustered histone 15 [KO:K11252]\n 8342 H2BC14; H2B clustered histone 14 [KO:K11252]\n 8343 H2BC7; H2B clustered histone 7 [KO:K11252]\n 8344 H2BC6; H2B clustered histone 6 [KO:K11252]\n 8345 H2BC9; H2B clustered histone 9 [KO:K11252]\n 8346 H2BC10; H2B clustered histone 10 [KO:K11252]\n 8347 H2BC4; H2B clustered histone 4 [KO:K11252]\n 8348 H2BC17; H2B clustered histone 17 [KO:K11252]\n 8349 H2BC21; H2B clustered histone 21 [KO:K11252]\n 8350 H3C1; H3 clustered histone 1 [KO:K11253]\n 8351 H3C4; H3 clustered histone 4 [KO:K11253]\n 8352 H3C3; H3 clustered histone 3 [KO:K11253]\n 8353 H3C6; H3 clustered histone 6 [KO:K11253]\n 8354 H3C11; H3 clustered histone 11 [KO:K11253]\n 8355 H3C8; H3 clustered histone 8 [KO:K11253]\n 8356 H3C12; H3 clustered histone 12 [KO:K11253]\n 8357 H3C10; H3 clustered histone 10 [KO:K11253]\n 8358 H3C2; H3 clustered histone 2 [KO:K11253]\n 8359 H4C1; H4 clustered histone 1 [KO:K11254]\n 8360 H4C4; H4 clustered histone 4 [KO:K11254]\n 8361 H4C6; H4 clustered histone 6 [KO:K11254]\n 8362 H4C12; H4 clustered histone 12 [KO:K11254]\n 8363 H4C11; H4 clustered histone 11 [KO:K11254]\n 8364 H4C3; H4 clustered histone 3 [KO:K11254]\n 8365 H4C8; H4 clustered histone 8 [KO:K11254]\n 8366 H4C2; H4 clustered histone 2 [KO:K11254]\n 8367 H4C5; H4 clustered histone 5 [KO:K11254]\n 8368 H4C13; H4 clustered histone 13 [KO:K11254]\n 8369 H4C7; H4 clustered histone 7 [KO:K11254]\n 8370 H4C14; H4 clustered histone 14 [KO:K11254]\n 83740 H2AB3; H2A.B variant histone 3 [KO:K11251]\n 85235 H2AC12; H2A clustered histone 12 [KO:K11251]\n 85236 H2BC12; H2B clustered histone 12 [KO:K11252]\n 87 ACTN1; actinin alpha 1 [KO:K05699]\n 8968 H3C7; H3 clustered histone 7 [KO:K11253]\n 8969 H2AC11; H2A clustered histone 11 [KO:K11251]\n 8970 H2BC11; H2B clustered histone 11 [KO:K11252]\n 92815 H2AC25; H2A clustered histone 25 [KO:K11251]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 94239 H2AZ2; H2A.Z variant histone 2 [KO:K11251]\n 9555 MACROH2A1; macroH2A.1 histone [KO:K11251]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\nCOMPOUND C00027 Hydrogen peroxide\n C00434 Double-stranded DNA\n C02737 Phosphatidylserine\nREFERENCE PMID:18305268\n AUTHORS Rahman A, Isenberg DA.\n TITLE Systemic lupus erythematosus.\n JOURNAL N Engl J Med 358:929-39 (2008)\n DOI:10.1056/NEJMra071297\nREFERENCE PMID:12835292\n AUTHORS Mok CC, Lau CS.\n TITLE Pathogenesis of systemic lupus erythematosus.\n JOURNAL J Clin Pathol 56:481-90 (2003)\n DOI:10.1136/jcp.56.7.481\nREFERENCE PMID:17943287\n AUTHORS Clatworthy MR, Smith KG.\n TITLE B cells in glomerulonephritis: focus on lupus nephritis.\n JOURNAL Semin Immunopathol 29:337-53 (2007)\n DOI:10.1007/s00281-007-0092-1\nREFERENCE PMID:8048228\n AUTHORS Couser WG.\n TITLE New insights into mechanisms of immune glomerular injury.\n JOURNAL West J Med 160:440-6 (1994)\nREFERENCE PMID:16932712\n AUTHORS Cook HT, Botto M.\n TITLE Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus.\n JOURNAL Nat Clin Pract Rheumatol 2:330-7 (2006)\n DOI:10.1038/ncprheum0191\nREFERENCE PMID:15459673\n AUTHORS Carroll MC.\n TITLE A protective role for innate immunity in systemic lupus erythematosus.\n JOURNAL Nat Rev Immunol 4:825-31 (2004)\n DOI:10.1038/nri1456\nREFERENCE PMID:15972354\n AUTHORS Sturfelt G, Truedsson L.\n TITLE Complement and its breakdown products in SLE.\n JOURNAL Rheumatology (Oxford) 44:1227-32 (2005)\n DOI:10.1093/rheumatology/keh719\nREFERENCE PMID:10430616\n AUTHORS Lu L, Kaliyaperumal A, Boumpas DT, Datta SK.\n TITLE Major peptide autoepitopes for nucleosome-specific T cells of human lupus.\n JOURNAL J Clin Invest 104:345-55 (1999)\n DOI:10.1172/JCI6801\nREFERENCE PMID:12965173\n AUTHORS Zieve GW, Khusial PR.\n TITLE The anti-Sm immune response in autoimmunity and cell biology.\n JOURNAL Autoimmun Rev 2:235-40 (2003)\n DOI:10.1016/S1568-9972(03)00018-1\nREFERENCE PMID:10025913\n AUTHORS Scofield RH, Farris AD, Horsfall AC, Harley JB.\n TITLE Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins.\n JOURNAL Arthritis Rheum 42:199-209 (1999)\n DOI:10.1002/1529-0131(199902)42:2<199::AID-ANR1>3.0.CO;2-1\nREFERENCE PMID:15380523\n AUTHORS Hoffman RW.\n TITLE T cells in the pathogenesis of systemic lupus erythematosus.\n JOURNAL Clin Immunol 113:4-13 (2004)\n DOI:10.1016/j.clim.2004.05.001\nREL_PATHWAY hsa04060 Cytokine-cytokine receptor interaction\n hsa04514 Cell adhesion molecules\n hsa04610 Complement and coagulation cascades\n hsa04612 Antigen processing and presentation\n hsa04630 JAK-STAT signaling pathway\n hsa04660 T cell receptor signaling pathway\n hsa04662 B cell receptor signaling pathway\n hsa04670 Leukocyte transendothelial migration\nKO_PATHWAY ko05322\n///\n\nENTRY hsa05323 Pathway\nNAME Rheumatoid arthritis - Homo sapiens (human)\nDESCRIPTION Rheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune system elevates pro-inflammatory cytokines and chemokines levels, which can promote synovial angiogenesis and leukocyte infiltration. The synovium forms a hyperplastic pannus with infiltrated macrophage-like and fibroblast-like synoviocytes and invades joints by secreting proteinases and inducing osteoclast differentiation.\nCLASS Human Diseases; Immune disease\nPATHWAY_MAP hsa05323 Rheumatoid arthritis\nDISEASE H00630 Rheumatoid arthritis\nDRUG D00742 Etanercept (USAN/INN)\n D02597 Adalimumab (USAN/INN)\n D02598 Infliximab (USAN/INN)\n D03203 Abatacept (USAN/INN)\n D03441 Certolizumab pegol (USAN/INN)\n D04358 Golimumab (USAN/INN)\n D08866 Baminercept (USAN/INN)\n D08955 Odanacatib (JAN/USAN)\n D09704 Atacicept (USAN/INN)\n D09967 Secukinumab (USAN/INN)\n D11020 Diclofenac etalhyaluronate sodium (JAN)\n D11121 Gimsilumab (USAN/INN)\n D11343 Otilimab (USAN)\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 101927180 ATP6V1FP2; V-type proton ATPase subunit F-like [KO:K02151]\n 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 10312 TCIRG1; T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154]\n 10673 TNFSF13B; TNF superfamily member 13b [KO:K05476]\n 127124 ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]\n 1435 CSF1; colony stimulating factor 1 [KO:K05453]\n 1437 CSF2; colony stimulating factor 2 [KO:K05427]\n 1493 CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]\n 1513 CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]\n 1514 CTSL; cathepsin L [KO:K01365] [EC:3.4.22.15]\n 155066 ATP6V0E2; ATPase H+ transporting V0 subunit e2 [KO:K02153]\n 2321 FLT1; fms related receptor tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]\n 2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]\n 23545 ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]\n 245972 ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]\n 245973 ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]\n 284 ANGPT1; angiopoietin 1 [KO:K05465]\n 2919 CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]\n 2920 CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505]\n 2921 CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490]\n 3458 IFNG; interferon gamma [KO:K04687]\n 3552 IL1A; interleukin 1 alpha [KO:K04383]\n 3553 IL1B; interleukin 1 beta [KO:K04519]\n 3569 IL6; interleukin 6 [KO:K05405]\n 3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]\n 3589 IL11; interleukin 11 [KO:K05417]\n 3600 IL15; interleukin 15 [KO:K05433]\n 3605 IL17A; interleukin 17A [KO:K05489]\n 3606 IL18; interleukin 18 [KO:K05482]\n 3683 ITGAL; integrin subunit alpha L [KO:K05718]\n 3689 ITGB2; integrin subunit beta 2 [KO:K06464]\n 3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]\n 4050 LTB; lymphotoxin beta [KO:K03157]\n 414062 CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]\n 4312 MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]\n 4314 MMP3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]\n 50617 ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]\n 51382 ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]\n 51561 IL23A; interleukin 23 subunit alpha [KO:K05426]\n 51606 ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]\n 523 ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:7.1.2.2]\n 525 ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]\n 526 ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]\n 527 ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]\n 528 ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]\n 529 ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]\n 533 ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]\n 534 ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]\n 535 ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]\n 537 ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]\n 54 ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]\n 5741 PTH; parathyroid hormone [KO:K05261]\n 6347 CCL2; C-C motif chemokine ligand 2 [KO:K14624]\n 6348 CCL3; C-C motif chemokine ligand 3 [KO:K05408]\n 6349 CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]\n 6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499]\n 6364 CCL20; C-C motif chemokine ligand 20 [KO:K14625]\n 6372 CXCL6; C-X-C motif chemokine ligand 6 [KO:K05506]\n 6374 CXCL5; C-X-C motif chemokine ligand 5 [KO:K05506]\n 6387 CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]\n 7010 TEK; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]\n 7040 TGFB1; transforming growth factor beta 1 [KO:K13375]\n 7042 TGFB2; transforming growth factor beta 2 [KO:K13376]\n 7043 TGFB3; transforming growth factor beta 3 [KO:K13377]\n 7097 TLR2; toll like receptor 2 [KO:K10159]\n 7099 TLR4; toll like receptor 4 [KO:K10160]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 7422 VEGFA; vascular endothelial growth factor A [KO:K05448]\n 8600 TNFSF11; TNF superfamily member 11 [KO:K05473]\n 8741 TNFSF13; TNF superfamily member 13 [KO:K05475]\n 8792 TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]\n 8992 ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153]\n 90423 ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]\n 9114 ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]\n 9296 ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 9550 ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]\nCOMPOUND C00080 H+\n C00584 Prostaglandin E2\n C05443 Vitamin D3\nREFERENCE PMID:16127012\n AUTHORS Zwerina J, Redlich K, Schett G, Smolen JS\n TITLE Pathogenesis of rheumatoid arthritis: targeting cytokines.\n JOURNAL Ann N Y Acad Sci 1051:716-29 (2005)\n DOI:10.1196/annals.1361.116\nREFERENCE PMID:20036936\n AUTHORS Szekanecz Z, Vegvari A, Szabo Z, Koch AE\n TITLE Chemokines and chemokine receptors in arthritis.\n JOURNAL Front Biosci (Schol Ed) 2:153-67 (2010)\n DOI:10.2741/53\nREFERENCE PMID:20651747\n AUTHORS Isaacs JD\n TITLE The changing face of rheumatoid arthritis: sustained remission for all?\n JOURNAL Nat Rev Immunol 10:605-11 (2010)\n DOI:10.1038/nri2804\nREFERENCE PMID:17195034\n AUTHORS Strand V, Kimberly R, Isaacs JD\n TITLE Biologic therapies in rheumatology: lessons learned, future directions.\n JOURNAL Nat Rev Drug Discov 6:75-92 (2007)\n DOI:10.1038/nrd2196\nREFERENCE PMID:20193003\n AUTHORS Bartok B, Firestein GS\n TITLE Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.\n JOURNAL Immunol Rev 233:233-55 (2010)\n DOI:10.1111/j.0105-2896.2009.00859.x\nREFERENCE PMID:17502360\n AUTHORS Dai SM, Shan ZZ, Xu H, Nishioka K\n TITLE Cellular targets of interleukin-18 in rheumatoid arthritis.\n JOURNAL Ann Rheum Dis 66:1411-8 (2007)\n DOI:10.1136/ard.2006.067793\nREFERENCE PMID:9627005\n AUTHORS Koch AE\n TITLE Review: angiogenesis: implications for rheumatoid arthritis.\n JOURNAL Arthritis Rheum 41:951-62 (1998)\n DOI:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D\nREFERENCE PMID:20305562\n AUTHORS Szekanecz Z, Besenyei T, Szentpetery A, Koch AE\n TITLE Angiogenesis and vasculogenesis in rheumatoid arthritis.\n JOURNAL Curr Opin Rheumatol 22:299-306 (2010)\n DOI:10.1097/BOR.0b013e328337c95a\nREFERENCE PMID:15059264\n AUTHORS Brunner-Weinzierl MC, Hoff H, Burmester GR\n TITLE Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.\n JOURNAL Arthritis Res Ther 6:45-54 (2004)\n DOI:10.1186/ar1158\nREFERENCE PMID:11861618\n AUTHORS Theill LE, Boyle WJ, Penninger JM\n TITLE RANK-L and RANK: T cells, bone loss, and mammalian evolution.\n JOURNAL Annu Rev Immunol 20:795-823 (2002)\n DOI:10.1146/annurev.immunol.20.100301.064753\nREFERENCE PMID:19184540\n AUTHORS Mensah KA, Li J, Schwarz EM\n TITLE The emerging field of osteoimmunology.\n JOURNAL Immunol Res 45:100-13 (2009)\n DOI:10.1007/s12026-009-8093-x\nREFERENCE PMID:16313349\n AUTHORS Takayanagi H, Sato K, Takaoka A, Taniguchi T\n TITLE Interplay between interferon and other cytokine systems in bone metabolism.\n JOURNAL Immunol Rev 208:181-93 (2005)\n DOI:10.1111/j.0105-2896.2005.00337.x\nREFERENCE PMID:20392226\n AUTHORS Takayanagi H\n TITLE New immune connections in osteoclast formation.\n JOURNAL Ann N Y Acad Sci 1192:117-23 (2010)\n DOI:10.1111/j.1749-6632.2009.05303.x\nREFERENCE PMID:19585227\n AUTHORS Nakashima T, Takayanagi H\n TITLE Osteoimmunology: crosstalk between the immune and bone systems.\n JOURNAL J Clin Immunol 29:555-67 (2009)\n DOI:10.1007/s10875-009-9316-6\nREFERENCE PMID:19455385\n AUTHORS Nakashima T, Takayanagi H\n TITLE Osteoclasts and the immune system.\n JOURNAL J Bone Miner Metab 27:519-29 (2009)\n DOI:10.1007/s00774-009-0089-z\nREFERENCE PMID:17380158\n AUTHORS Takayanagi H\n TITLE Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.\n JOURNAL Nat Rev Immunol 7:292-304 (2007)\n DOI:10.1038/nri2062\nREFERENCE PMID:20510236\n AUTHORS Fox DA, Gizinski A, Morgan R, Lundy SK\n TITLE Cell-cell interactions in rheumatoid arthritis synovium.\n JOURNAL Rheum Dis Clin North Am 36:311-23 (2010)\n DOI:10.1016/j.rdc.2010.02.004\nREFERENCE PMID:15055519\n AUTHORS Rho J, Takami M, Choi Y\n TITLE Osteoimmunology: interactions of the immune and skeletal systems.\n JOURNAL Mol Cells 17:1-9 (2004)\nREL_PATHWAY hsa04370 VEGF signaling pathway\n hsa04380 Osteoclast differentiation\n hsa04620 Toll-like receptor signaling pathway\n hsa04659 Th17 cell differentiation\n hsa04660 T cell receptor signaling pathway\n hsa04670 Leukocyte transendothelial migration\nKO_PATHWAY ko05323\n///\n\nENTRY hsa05330 Pathway\nNAME Allograft rejection - Homo sapiens (human)\nDESCRIPTION Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft.\nCLASS Human Diseases; Immune disease\nPATHWAY_MAP hsa05330 Allograft rejection\nDISEASE H00083 Allograft rejection\nDRUG D03222 Belatacept (USAN/INN)\n D06071 Teneliximab (USAN/INN)\n D11357 Bleselumab (USAN/INN)\n D11610 Iscalimab (USAN/INN)\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 3002 GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3458 IFNG; interferon gamma [KO:K04687]\n 355 FAS; Fas cell surface death receptor [KO:K04390]\n 3558 IL2; interleukin 2 [KO:K05429]\n 356 FASLG; Fas ligand [KO:K04389]\n 3565 IL4; interleukin 4 [KO:K05430]\n 3567 IL5; interleukin 5 [KO:K05428]\n 3586 IL10; interleukin 10 [KO:K05443]\n 3592 IL12A; interleukin 12A [KO:K05406]\n 3593 IL12B; interleukin 12B [KO:K05425]\n 5551 PRF1; perforin 1 [KO:K07818]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\nCOMPOUND C00533 Nitric oxide\nREFERENCE PMID:10746853\n AUTHORS Arakelov A, Lakkis FG.\n TITLE The alloimmune response and effector mechanisms of allograft rejection.\n JOURNAL Semin Nephrol 20:95-102 (2000)\nREFERENCE PMID:12023610\n AUTHORS Le Moine A, Goldman M, Abramowicz D.\n TITLE Multiple pathways to allograft rejection.\n JOURNAL Transplantation 73:1373-81 (2002)\n DOI:10.1097/00007890-200205150-00001\nREFERENCE PMID:17445565\n AUTHORS Trivedi HL.\n TITLE Immunobiology of rejection and adaptation.\n JOURNAL Transplant Proc 39:647-52 (2007)\n DOI:10.1016/j.transproceed.2007.01.047\nREFERENCE PMID:14710779\n AUTHORS Pietra BA.\n TITLE Transplantation immunology 2003: simplified approach.\n JOURNAL Pediatr Clin North Am 50:1233-59 (2003)\n DOI:10.1016/S0031-3955(03)00119-6\nREFERENCE PMID:8835634\n AUTHORS Oka T, Yoshimura N.\n TITLE Immunosuppression in organ transplantation.\n JOURNAL Jpn J Pharmacol 71:89-100 (1996)\n DOI:10.1254/jjp.71.89\nREFERENCE PMID:10571983\n AUTHORS Sayegh MH.\n TITLE Why do we reject a graft? Role of indirect allorecognition in graft rejection.\n JOURNAL Kidney Int 56:1967-79 (1999)\n DOI:10.1046/j.1523-1755.1999.00751.x\nREFERENCE PMID:10331992\n AUTHORS Benichou G.\n TITLE Direct and indirect antigen recognition: the pathways to allograft immune rejection.\n JOURNAL Front Biosci 4:D476-80 (1999)\n DOI:10.2741/benichou\nREFERENCE PMID:10667806\n AUTHORS Turvey SE, Wood KJ.\n TITLE Immunobiology of solid organ transplantation.\n JOURNAL Int Surg 84:279-90 (1999)\nREFERENCE \n AUTHORS Janeway CA, Travers P, Walport M, Shlomchik MJ.\n TITLE Immunobiology 6th edition\n JOURNAL Garland Science Publishing (2005)\nREFERENCE PMID:12216939\n AUTHORS Game DS, Lechler RI.\n TITLE Pathways of allorecognition: implications for transplantation tolerance.\n JOURNAL Transpl Immunol 10:101-8 (2002)\n DOI:10.1016/S0966-3274(02)00055-2\nREFERENCE PMID:12563298\n AUTHORS Lechler RI, Garden OA, Turka LA.\n TITLE The complementary roles of deletion and regulation in transplantation tolerance.\n JOURNAL Nat Rev Immunol 3:147-58 (2003)\n DOI:10.1038/nri1002\nREL_PATHWAY hsa04210 Apoptosis\n hsa04514 Cell adhesion molecules\n hsa04610 Complement and coagulation cascades\n hsa04612 Antigen processing and presentation\n hsa04660 T cell receptor signaling pathway\n hsa04662 B cell receptor signaling pathway\nKO_PATHWAY ko05330\n///\n\nENTRY hsa05332 Pathway\nNAME Graft-versus-host disease - Homo sapiens (human)\nDESCRIPTION Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.\nCLASS Human Diseases; Immune disease\nPATHWAY_MAP hsa05332 Graft-versus-host disease\nDISEASE H00084 Graft-versus-host disease\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 112268355 [KO:K07980]\n 115653 KIR3DL3; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3 [KO:K07980]\n 3002 GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3458 IFNG; interferon gamma [KO:K04687]\n 355 FAS; Fas cell surface death receptor [KO:K04390]\n 3552 IL1A; interleukin 1 alpha [KO:K04383]\n 3553 IL1B; interleukin 1 beta [KO:K04519]\n 3558 IL2; interleukin 2 [KO:K05429]\n 356 FASLG; Fas ligand [KO:K04389]\n 3569 IL6; interleukin 6 [KO:K05405]\n 3802 KIR2DL1; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1 [KO:K07981]\n 3803 KIR2DL2; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 2 [KO:K07981]\n 3804 KIR2DL3; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3 [KO:K07981]\n 3811 KIR3DL1; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1 [KO:K07980]\n 3812 KIR3DL2; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2 [KO:K07980]\n 3813 KIR3DS1; killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1 [KO:K07980]\n 3821 KLRC1; killer cell lectin like receptor C1 [KO:K06541]\n 3824 KLRD1; killer cell lectin like receptor D1 [KO:K06516]\n 5551 PRF1; perforin 1 [KO:K07818]\n 57292 KIR2DL5A; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5A [KO:K24232]\n 7124 TNF; tumor necrosis factor [KO:K03156]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\nCOMPOUND C00338 Lipopolysaccharide\n C00533 Nitric oxide\nREFERENCE PMID:16412784\n AUTHORS Ferrara JL, Reddy P.\n TITLE Pathophysiology of graft-versus-host disease.\n JOURNAL Semin Hematol 43:3-10 (2006)\n DOI:10.1053/j.seminhematol.2005.09.001\nREFERENCE PMID:14735553\n AUTHORS Reddy P.\n TITLE Pathophysiology of acute graft-versus-host disease.\n JOURNAL Hematol Oncol 21:149-61 (2003)\n DOI:10.1002/hon.716\nREFERENCE PMID:17900507\n AUTHORS Sun Y, Tawara I, Toubai T, Reddy P.\n TITLE Pathophysiology of acute graft-versus-host disease: recent advances.\n JOURNAL Transl Res 150:197-214 (2007)\n DOI:10.1016/j.trsl.2007.06.003\nREFERENCE PMID:15882431\n AUTHORS Jaksch M, Mattsson J.\n TITLE The pathophysiology of acute graft-versus-host disease.\n JOURNAL Scand J Immunol 61:398-409 (2005)\n DOI:10.1111/j.1365-3083.2005.01595.x\nREFERENCE PMID:12359826\n AUTHORS Vogelsang GB, Lee L, Bensen-Kennedy DM.\n TITLE Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.\n JOURNAL Annu Rev Med 54:29-52 (2003)\n DOI:10.1146/annurev.med.54.101601.152339\nREFERENCE PMID:14556773\n AUTHORS Reddy P, Ferrara JL.\n TITLE Immunobiology of acute graft-versus-host disease.\n JOURNAL Blood Rev 17:187-94 (2003)\n DOI:10.1016/S0268-960X(03)00009-2\nREFERENCE PMID:16147539\n AUTHORS Blazar BR, Murphy WJ.\n TITLE Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).\n JOURNAL Philos Trans R Soc Lond B Biol Sci 360:1747-67 (2005)\n DOI:10.1098/rstb.2005.1701\nREFERENCE PMID:15372473\n AUTHORS Couriel D, Caldera H, Champlin R, Komanduri K.\n TITLE Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.\n JOURNAL Cancer 101:1936-46 (2004)\n DOI:10.1002/cncr.20613\nREFERENCE PMID:17784964\n AUTHORS Jacobsohn DA, Vogelsang GB.\n TITLE Acute graft versus host disease.\n JOURNAL Orphanet J Rare Dis 2:35 (2007)\n DOI:10.1186/1750-1172-2-35\nREL_PATHWAY hsa04060 Cytokine-cytokine receptor interaction\n hsa04210 Apoptosis\n hsa04514 Cell adhesion molecules\n hsa04612 Antigen processing and presentation\n hsa04620 Toll-like receptor signaling pathway\n hsa04650 Natural killer cell mediated cytotoxicity\n hsa04660 T cell receptor signaling pathway\nKO_PATHWAY ko05332\n///\n\nENTRY hsa05416 Pathway\nNAME Viral myocarditis - Homo sapiens (human)\nDESCRIPTION Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is still considered the dominant etiological agent. Myocarditis may be caused by direct cytopathic effects of virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. The virus enters the myocyte through internalization of the coxsackie-adenoviral receptor (CAR) and its coreceptor, decay-accelerating factor (DAF). Viral proteases cleave various proteins in the host cell. One example is viral protease 2A, which cleaves eukaryote initiation factor 4G (eIF4G) and the dystrophin protein, resulting in a complete shutdown of cap-dependent RNA translation and cytoskeletal destruction in infected cardiomyocytes, respectively. CVB3 also cleaves the member of the Bcl-2 family Bid, leading to apoptosis. CVB3 infection also induces the cleavage of cyclin D protein through a proteasome-dependent pathway, leading to the host cell-growth arrest. Viral infection and necrosis of myocytes may lead to the release of intracellular antigens, resulting in activation of self-reactive T cells. CVB infection is a significant cause of dilated cardiomyopathy (DCM) as well as myocarditis. Epidemiologically, myocarditis underlies a significant portion of patients with DCM.\nCLASS Human Diseases; Cardiovascular disease\nPATHWAY_MAP hsa05416 Viral myocarditis\nDISEASE H00295 Viral myocarditis\nORGANISM Homo sapiens (human) [GN:hsa]\nGENE 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]\n 137868 SGCZ; sarcoglycan zeta [KO:K27062]\n 1525 CXADR; CXADR Ig-like cell adhesion molecule [KO:K06788]\n 1604 CD55; CD55 molecule (Cromer blood group) [KO:K04006]\n 1605 DAG1; dystroglycan 1 [KO:K06265]\n 1756 DMD; dystrophin [KO:K10366]\n 1837 DTNA; dystrobrevin alpha [KO:K26998]\n 1981 EIF4G1; eukaryotic translation initiation factor 4 gamma 1 [KO:K03260]\n 1982 EIF4G2; eukaryotic translation initiation factor 4 gamma 2 [KO:K03260]\n 25 ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]\n 2534 FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]\n 27 ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2]\n 284217 LAMA1; laminin subunit alpha 1 [KO:K05637]\n 3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751]\n 3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751]\n 3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751]\n 3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]\n 3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]\n 3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]\n 3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]\n 3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]\n 3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]\n 3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]\n 3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]\n 3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]\n 3120 HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]\n 3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]\n 3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]\n 3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]\n 3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]\n 3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]\n 3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751]\n 3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751]\n 3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751]\n 3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490]\n 3683 ITGAL; integrin subunit alpha L [KO:K05718]\n 3689 ITGB2; integrin subunit beta 2 [KO:K06464]\n 3908 LAMA2; laminin subunit alpha 2 [KO:K05637]\n 4624 MYH6; myosin heavy chain 6 [KO:K17751]\n 4625 MYH7; myosin heavy chain 7 [KO:K17751]\n 4842 NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]\n 54205 CYCS; cytochrome c, somatic [KO:K08738]\n 5551 PRF1; perforin 1 [KO:K07818]\n 5879 RAC1; Rac family small GTPase 1 [KO:K04392]\n 5880 RAC2; Rac family small GTPase 2 [KO:K07860]\n 5881 RAC3; Rac family small GTPase 3 [KO:K07861]\n 595 CCND1; cyclin D1 [KO:K04503]\n 60 ACTB; actin beta [KO:K05692]\n 637 BID; BH3 interacting domain death agonist [KO:K04726]\n 6442 SGCA; sarcoglycan alpha [KO:K12565]\n 6443 SGCB; sarcoglycan beta [KO:K12566]\n 6444 SGCD; sarcoglycan delta [KO:K12563]\n 6445 SGCG; sarcoglycan gamma [KO:K12564]\n 6640 SNTA1; syntrophin alpha 1 [KO:K24063]\n 6641 SNTB1; syntrophin beta 1 [KO:K24064]\n 6645 SNTB2; syntrophin beta 2 [KO:K24064]\n 71 ACTG1; actin gamma 1 [KO:K05692]\n 8082 SSPN; sarcospan [KO:K22194]\n 836 CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]\n 841 CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]\n 842 CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]\n 857 CAV1; caveolin 1 [KO:K06278]\n 859 CAV3; caveolin 3 [KO:K12959]\n 8672 EIF4G3; eukaryotic translation initiation factor 4 gamma 3 [KO:K03260]\n 8910 SGCE; sarcoglycan epsilon [KO:K27061]\n 940 CD28; CD28 molecule [KO:K06470]\n 941 CD80; CD80 molecule [KO:K05412]\n 942 CD86; CD86 molecule [KO:K05413]\n 958 CD40; CD40 molecule [KO:K03160]\n 959 CD40LG; CD40 ligand [KO:K03161]\nREFERENCE PMID:18039131\n AUTHORS Esfandiarei M, McManus BM\n TITLE Molecular biology and pathogenesis of viral myocarditis.\n JOURNAL Annu Rev Pathol 3:127-55 (2008)\n DOI:10.1146/annurev.pathmechdis.3.121806.151534\nREFERENCE PMID:12920582\n AUTHORS Badorff C, Knowlton KU\n TITLE Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside.\n JOURNAL Med Microbiol Immunol 193:121-6 (2004)\n DOI:10.1007/s00430-003-0189-7\nREFERENCE PMID:17200452\n AUTHORS Maekawa Y, Ouzounian M, Opavsky MA, Liu PP\n TITLE Connecting the missing link between dilated cardiomyopathy and viral myocarditis: virus, cytoskeleton, and innate immunity.\n JOURNAL Circulation 115:5-8 (2007)\n DOI:10.1161/CIRCULATIONAHA.106.670554\nREFERENCE PMID:12439638\n AUTHORS Pankuweit S, Portig I, Maisch B\n TITLE Pathophysiology of cardiac inflammation: molecular mechanisms.\n JOURNAL Herz 27:669-76 (2002)\n DOI:10.1007/s00059-002-2421-4\nREFERENCE PMID:16845885\n AUTHORS Gao G, Luo H\n TITLE The ubiquitin-proteasome pathway in viral infections.\n JOURNAL Can J Physiol Pharmacol 84:5-14 (2006)\n DOI:10.1139/y05-144\nREFERENCE PMID:16413486\n AUTHORS Coyne CB, Bergelson JM\n TITLE Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions.\n JOURNAL Cell 124:119-31 (2006)\n DOI:10.1016/j.cell.2005.10.035\nREFERENCE PMID:10904843\n AUTHORS Badorff C, Lee GH, Knowlton KU\n TITLE Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.\n JOURNAL Herz 25:227-32 (2000)\n DOI:10.1007/s000590050011\nREFERENCE PMID:18357777\n AUTHORS Knowlton KU\n TITLE CVB infection and mechanisms of viral cardiomyopathy.\n JOURNAL Curr Top Microbiol Immunol 323:315-35 (2008)\n DOI:10.1007/978-3-540-75546-3_15\nREFERENCE PMID:18545064\n AUTHORS Castellano G, Affuso F, Di Conza P, Fazio S\n TITLE Myocarditis and dilated cardiomyopathy: possible connections and treatments.\n JOURNAL J Cardiovasc Med (Hagerstown) 9:666-71 (2008)\n DOI:10.2459/JCM.0b013e3282f3e9c2\nREFERENCE PMID:19357408\n AUTHORS Cooper LT Jr\n TITLE Myocarditis.\n JOURNAL N Engl J Med 360:1526-38 (2009)\n DOI:10.1056/NEJMra0800028\nREFERENCE PMID:10051305\n AUTHORS Kawai C\n TITLE From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future.\n JOURNAL Circulation 99:1091-100 (1999)\n DOI:10.1161/01.CIR.99.8.1091\nREFERENCE PMID:11524405\n AUTHORS Liu PP, Mason JW\n TITLE Advances in the understanding of myocarditis.\n JOURNAL Circulation 104:1076-82 (2001)\n DOI:10.1161/hc3401.095198\nREFERENCE PMID:14522402\n AUTHORS Mason JW\n TITLE Myocarditis and dilated cardiomyopathy: an inflammatory link.\n JOURNAL Cardiovasc Res 60:5-10 (2003)\n DOI:10.1016/S0008-6363(03)00437-1\nREFERENCE PMID:16817756\n AUTHORS Tam PE\n TITLE Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.\n JOURNAL Viral Immunol 19:133-46 (2006)\n DOI:10.1089/vim.2006.19.133\nREL_PATHWAY hsa03050 Proteasome\n hsa04110 Cell cycle\n hsa04210 Apoptosis\n hsa04260 Cardiac muscle contraction\n hsa04512 ECM-receptor interaction\n hsa04612 Antigen processing and presentation\n hsa04660 T cell receptor signaling pathway\n hsa05414 Dilated cardiomyopathy\nKO_PATHWAY ko05416\n///")
6. └─ffrec$setBody(value)
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