KEGG   PATHWAY: ko05323
Entry
ko05323                     Pathway                                
Name
Rheumatoid arthritis
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
ko05323  Rheumatoid arthritis
ko05323

Disease
H00630  Rheumatoid arthritis
Orthology
K01365  CTSL; cathepsin L [EC:3.4.22.15]
K01371  CTSK; cathepsin K [EC:3.4.22.38]
K01388  MMP1; matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7]
K01394  MMP3; matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17]
K02144  ATPeV1H; V-type H+-transporting ATPase subunit H
K02145  ATPeV1A, ATP6A; V-type H+-transporting ATPase subunit A [EC:7.1.2.2]
K02146  ATPeV0D, ATP6D; V-type H+-transporting ATPase subunit d
K02147  ATPeV1B, ATP6B; V-type H+-transporting ATPase subunit B
K02148  ATPeV1C, ATP6C; V-type H+-transporting ATPase subunit C
K02149  ATPeV1D, ATP6M; V-type H+-transporting ATPase subunit D
K02150  ATPeV1E, ATP6E; V-type H+-transporting ATPase subunit E
K02151  ATPeV1F, ATP6S14; V-type H+-transporting ATPase subunit F
K02152  ATPeV1G, ATP6G; V-type H+-transporting ATPase subunit G
K02153  ATPeV0E, ATP6H; V-type H+-transporting ATPase subunit e
K02154  ATPeV0A, ATP6N; V-type H+-transporting ATPase subunit a
K02155  ATPeV0C, ATP6L; V-type H+-transporting ATPase 16kDa proteolipid subunit
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03157  LTB, TNFC; lymphotoxin beta (TNF superfamily, member 3)
K03661  ATPeV0B, ATP6F; V-type H+-transporting ATPase 21kDa proteolipid subunit
K03662  ATPeVS1, ATP6S1; V-type H+-transporting ATPase S1 subunit
K04379  FOS; proto-oncogene protein c-fos
K04383  IL1A; interleukin 1 alpha
K04448  JUN; transcription factor AP-1
K04519  IL1B; interleukin 1 beta
K04687  IFNG; interferon gamma
K05096  FLT1, VEGFR1; FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05121  TEK, TIE2, CD202; endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05147  TNFRSF11A, RANK, CD265; tumor necrosis factor receptor superfamily member 11A
K05261  PTH; parathyroid hormone
K05405  IL6; interleukin 6
K05408  CCL3; C-C motif chemokine 3
K05412  CD80; CD80 antigen
K05413  CD86; CD86 antigen
K05417  IL11; interleukin 11
K05426  IL23A; interleukin 23 subunit alpha
K05427  CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor
K05433  IL15; interleukin 15
K05448  VEGFA; vascular endothelial growth factor A
K05453  CSF1, MCSF; macrophage colony-stimulating factor 1
K05465  ANGPT1; angiopoietin 1
K05473  TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K05475  TNFSF13, APRIL, CD256; tumor necrosis factor ligand superfamily member 13
K05476  TNFSF13B, TNFSF20, CD257; tumor necrosis factor ligand superfamily member 13B
K05482  IL18, IL1F4; interleukin 18
K05489  IL17A, CTLA8; interleukin 17A
K05505  CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3
K05506  CXCL5_6, SCYB5_6; C-X-C motif chemokine 5/6
K05718  ITGAL, CD11a; integrin alpha L
K06464  ITGB2, CD18; integrin beta 2
K06470  CD28; CD28 antigen
K06490  ICAM1, CD54; intercellular adhesion molecule 1
K06538  CTLA4, CD152; cytotoxic T-lymphocyte-associated protein 4
K06752  MHC2; MHC class II antigen
K06856  IGH; immunoglobulin heavy chain
K10030  IL8, CXCL8; interleukin 8
K10031  CXCL12; C-X-C motif chemokine 12
K10159  TLR2, CD282; toll-like receptor 2
K10160  TLR4, CD284; toll-like receptor 4
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K12499  CCL5; C-C motif chemokine 5
K13375  TGFB1; transforming growth factor beta-1
K13376  TGFB2; transforming growth factor beta-2
K13377  TGFB3; transforming growth factor beta-3
K14379  ACP5; tartrate-resistant acid phosphatase type 5 [EC:3.1.3.2]
K14624  CCL2, MCP1; C-C motif chemokine 2
K14625  CCL20; C-C motif chemokine 20
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
ko04370  VEGF signaling pathway
ko04380  Osteoclast differentiation
ko04620  Toll-like receptor signaling pathway
ko04659  Th17 cell differentiation
ko04660  T cell receptor signaling pathway
ko04670  Leukocyte transendothelial migration

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