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KEGG   PATHWAY: hsa05323
Entry
hsa05323                    Pathway                                
Name
Rheumatoid arthritis - Homo sapiens (human)
Description
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.
Class
Human Diseases; Immune disease
Pathway map
hsa05323  Rheumatoid arthritis
hsa05323

Disease
H00630  Rheumatoid arthritis
Drug
D00742  Etanercept (USAN/INN)
D02597  Adalimumab (USAN/INN)
D02598  Infliximab (USAN/INN)
D03203  Abatacept (USAN/INN)
D03441  Certolizumab pegol (USAN/INN)
D04358  Golimumab (USAN/INN)
D08866  Baminercept (USAN/INN)
D08955  Odanacatib (JAN/USAN)
D09704  Atacicept (USAN/INN)
D09967  Secukinumab (USAN/INN)
D11020  Diclofenac etalhyaluronate sodium (JAN)
D11121  Gimsilumab (USAN/INN)
D11343  Otilimab (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
940  CD28; CD28 molecule [KO:K06470]
1493  CTLA4; cytotoxic T-lymphocyte associated protein 4 [KO:K06538]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
3683  ITGAL; integrin subunit alpha L [KO:K05718]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
3383  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
3600  IL15; interleukin 15 [KO:K05433]
8741  TNFSF13; TNF superfamily member 13 [KO:K05475]
10673  TNFSF13B; TNF superfamily member 13b [KO:K05476]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
4050  LTB; lymphotoxin beta [KO:K03157]
7124  TNF; tumor necrosis factor [KO:K03156]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
3569  IL6; interleukin 6 [KO:K05405]
3589  IL11; interleukin 11 [KO:K05417]
3606  IL18; interleukin 18 [KO:K05482]
7097  TLR2; toll like receptor 2 [KO:K10159]
7099  TLR4; toll like receptor 4 [KO:K10160]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  TGFB3; transforming growth factor beta 3 [KO:K13377]
51561  IL23A; interleukin 23 subunit alpha [KO:K05426]
3605  IL17A; interleukin 17A [KO:K05489]
5741  PTH; parathyroid hormone [KO:K05261]
1435  CSF1; colony stimulating factor 1 [KO:K05453]
8600  TNFSF11; TNF superfamily member 11 [KO:K05473]
8792  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
523  ATP6V1A; ATPase H+ transporting V1 subunit A [KO:K02145] [EC:7.1.2.2]
525  ATP6V1B1; ATPase H+ transporting V1 subunit B1 [KO:K02147]
526  ATP6V1B2; ATPase H+ transporting V1 subunit B2 [KO:K02147]
245973  ATP6V1C2; ATPase H+ transporting V1 subunit C2 [KO:K02148]
528  ATP6V1C1; ATPase H+ transporting V1 subunit C1 [KO:K02148]
51382  ATP6V1D; ATPase H+ transporting V1 subunit D [KO:K02149]
90423  ATP6V1E2; ATPase H+ transporting V1 subunit E2 [KO:K02150]
529  ATP6V1E1; ATPase H+ transporting V1 subunit E1 [KO:K02150]
9296  ATP6V1F; ATPase H+ transporting V1 subunit F [KO:K02151]
101927180  ATP6V1FP2; V-type proton ATPase subunit F-like [KO:K02151]
9550  ATP6V1G1; ATPase H+ transporting V1 subunit G1 [KO:K02152]
127124  ATP6V1G3; ATPase H+ transporting V1 subunit G3 [KO:K02152]
534  ATP6V1G2; ATPase H+ transporting V1 subunit G2 [KO:K02152]
8992  ATP6V0E1; ATPase H+ transporting V0 subunit e1 [KO:K02153]
155066  ATP6V0E2; ATPase H+ transporting V0 subunit e2 [KO:K02153]
10312  TCIRG1; T cell immune regulator 1, ATPase H+ transporting V0 subunit a3 [KO:K02154]
23545  ATP6V0A2; ATPase H+ transporting V0 subunit a2 [KO:K02154]
50617  ATP6V0A4; ATPase H+ transporting V0 subunit a4 [KO:K02154]
535  ATP6V0A1; ATPase H+ transporting V0 subunit a1 [KO:K02154]
9114  ATP6V0D1; ATPase H+ transporting V0 subunit d1 [KO:K02146]
245972  ATP6V0D2; ATPase H+ transporting V0 subunit d2 [KO:K02146]
51606  ATP6V1H; ATPase H+ transporting V1 subunit H [KO:K02144]
537  ATP6AP1; ATPase H+ transporting accessory protein 1 [KO:K03662]
527  ATP6V0C; ATPase H+ transporting V0 subunit c [KO:K02155]
533  ATP6V0B; ATPase H+ transporting V0 subunit b [KO:K03661]
1513  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
54  ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
4312  MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]
4314  MMP3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]
1514  CTSL; cathepsin L [KO:K01365] [EC:3.4.22.15]
1437  CSF2; colony stimulating factor 2 [KO:K05427]
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
6347  CCL2; C-C motif chemokine ligand 2 [KO:K14624]
6348  CCL3; C-C motif chemokine ligand 3 [KO:K05408]
6349  CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]
414062  CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]
6364  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
2919  CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]
2920  CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505]
2921  CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505]
6374  CXCL5; C-X-C motif chemokine ligand 5 [KO:K05506]
6372  CXCL6; C-X-C motif chemokine ligand 6 [KO:K05506]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
6387  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
7422  VEGFA; vascular endothelial growth factor A [KO:K05448]
2321  FLT1; fms related receptor tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
284  ANGPT1; angiopoietin 1 [KO:K05465]
7010  TEK; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]
3458  IFNG; interferon gamma [KO:K04687]
Compound
C00080  H+
C00584  Prostaglandin E2
C05443  Vitamin D3
Reference
PMID:16127012
  Authors
Zwerina J, Redlich K, Schett G, Smolen JS
  Title
Pathogenesis of rheumatoid arthritis: targeting cytokines.
  Journal
Ann N Y Acad Sci 1051:716-29 (2005)
DOI:10.1196/annals.1361.116
Reference
PMID:20036936
  Authors
Szekanecz Z, Vegvari A, Szabo Z, Koch AE
  Title
Chemokines and chemokine receptors in arthritis.
  Journal
Front Biosci (Schol Ed) 2:153-67 (2010)
DOI:10.2741/53
Reference
PMID:20651747
  Authors
Isaacs JD
  Title
The changing face of rheumatoid arthritis: sustained remission for all?
  Journal
Nat Rev Immunol 10:605-11 (2010)
DOI:10.1038/nri2804
Reference
PMID:17195034
  Authors
Strand V, Kimberly R, Isaacs JD
  Title
Biologic therapies in rheumatology: lessons learned, future directions.
  Journal
Nat Rev Drug Discov 6:75-92 (2007)
DOI:10.1038/nrd2196
Reference
PMID:20193003
  Authors
Bartok B, Firestein GS
  Title
Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.
  Journal
Immunol Rev 233:233-55 (2010)
DOI:10.1111/j.0105-2896.2009.00859.x
Reference
PMID:17502360
  Authors
Dai SM, Shan ZZ, Xu H, Nishioka K
  Title
Cellular targets of interleukin-18 in rheumatoid arthritis.
  Journal
Ann Rheum Dis 66:1411-8 (2007)
DOI:10.1136/ard.2006.067793
Reference
PMID:9627005
  Authors
Koch AE
  Title
Review: angiogenesis: implications for rheumatoid arthritis.
  Journal
Arthritis Rheum 41:951-62 (1998)
DOI:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D
Reference
PMID:20305562
  Authors
Szekanecz Z, Besenyei T, Szentpetery A, Koch AE
  Title
Angiogenesis and vasculogenesis in rheumatoid arthritis.
  Journal
Curr Opin Rheumatol 22:299-306 (2010)
DOI:10.1097/BOR.0b013e328337c95a
Reference
PMID:15059264
  Authors
Brunner-Weinzierl MC, Hoff H, Burmester GR
  Title
Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
  Journal
Arthritis Res Ther 6:45-54 (2004)
DOI:10.1186/ar1158
Reference
PMID:11861618
  Authors
Theill LE, Boyle WJ, Penninger JM
  Title
RANK-L and RANK: T cells, bone loss, and mammalian evolution.
  Journal
Annu Rev Immunol 20:795-823 (2002)
DOI:10.1146/annurev.immunol.20.100301.064753
Reference
PMID:19184540
  Authors
Mensah KA, Li J, Schwarz EM
  Title
The emerging field of osteoimmunology.
  Journal
Immunol Res 45:100-13 (2009)
DOI:10.1007/s12026-009-8093-x
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:19455385
  Authors
Nakashima T, Takayanagi H
  Title
Osteoclasts and the immune system.
  Journal
J Bone Miner Metab 27:519-29 (2009)
DOI:10.1007/s00774-009-0089-z
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20510236
  Authors
Fox DA, Gizinski A, Morgan R, Lundy SK
  Title
Cell-cell interactions in rheumatoid arthritis synovium.
  Journal
Rheum Dis Clin North Am 36:311-23 (2010)
DOI:10.1016/j.rdc.2010.02.004
Reference
PMID:15055519
  Authors
Rho J, Takami M, Choi Y
  Title
Osteoimmunology: interactions of the immune and skeletal systems.
  Journal
Mol Cells 17:1-9 (2004)
Related
pathway
hsa04370  VEGF signaling pathway
hsa04380  Osteoclast differentiation
hsa04620  Toll-like receptor signaling pathway
hsa04659  Th17 cell differentiation
hsa04660  T cell receptor signaling pathway
hsa04670  Leukocyte transendothelial migration
KO pathway
ko05323   

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Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (94)   
   KEGG GENES (94)   
All databases (96)   

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