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
K05412  CD80 antigen
K05413  CD86 antigen
K06470  CD28 antigen
K06538  cytotoxic T-lymphocyte-associated protein 4
K06752  MHC class II antigen
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K05718  integrin alpha L
K06464  integrin beta 2
K06490  intercellular adhesion molecule 1
K05433  interleukin 15
K05475  tumor necrosis factor ligand superfamily member 13
K05476  tumor necrosis factor ligand superfamily member 13B
K06856  immunoglobulin heavy chain
K03157  lymphotoxin beta (TNF superfamily, member 3)
K03156  tumor necrosis factor superfamily, member 2
K04383  interleukin 1 alpha
K04519  interleukin 1 beta
K05405  interleukin 6
K05417  interleukin 11
K05482  interleukin 18
K10159  toll-like receptor 2
K10160  toll-like receptor 4
K04448  transcription factor AP-1
K04379  proto-oncogene protein c-fos
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K05426  interleukin 23 subunit alpha
K05489  interleukin 17A
K05261  parathyroid hormone
K05453  macrophage colony-stimulating factor 1
K05473  tumor necrosis factor ligand superfamily member 11
K05147  tumor necrosis factor receptor superfamily member 11A
K02145  V-type H+-transporting ATPase subunit A [EC:7.1.2.2]
K02147  V-type H+-transporting ATPase subunit B
K02148  V-type H+-transporting ATPase subunit C
K02149  V-type H+-transporting ATPase subunit D
K02150  V-type H+-transporting ATPase subunit E
K02151  V-type H+-transporting ATPase subunit F
K02152  V-type H+-transporting ATPase subunit G
K02153  V-type H+-transporting ATPase subunit e
K02154  V-type H+-transporting ATPase subunit a
K02146  V-type H+-transporting ATPase subunit d
K02144  V-type H+-transporting ATPase subunit H
K03662  V-type H+-transporting ATPase S1 subunit
K02155  V-type H+-transporting ATPase 16kDa proteolipid subunit
K03661  V-type H+-transporting ATPase 21kDa proteolipid subunit
K01371  cathepsin K [EC:3.4.22.38]
K14379  tartrate-resistant acid phosphatase type 5 [EC:3.1.3.2]
K01388  matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7]
K01394  matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17]
K01365  cathepsin L [EC:3.4.22.15]
K05427  granulocyte-macrophage colony-stimulating factor
K12499  C-C motif chemokine 5
K14624  C-C motif chemokine 2
K05408  C-C motif chemokine 3
K14625  C-C motif chemokine 20
K05505  C-X-C motif chemokine 1/2/3
K05506  C-X-C motif chemokine 5/6
K10030  interleukin 8
K10031  C-X-C motif chemokine 12
K05448  vascular endothelial growth factor A
K05096  FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05465  angiopoietin 1
K05121  endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K04687  interferon gamma
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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