KEGG PATHWAY: hsa05323

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 diseases

Pathway map

hsa05323

Rheumatoid arthritis

Disease

H00436	Osteopetrosis
H00630	Rheumatoid arthritis

Drug

D00742	Etanercept (genetical recombination) (JAN)
D02597	Adalimumab (genetical recombination) (JAN)
D02598	Infliximab (genetical recombination) (JAN)
D03068	Belimumab (genetical recombination) (JAN)
D03203	Abatacept (genetical recombination) (JAN)
D03222	Belatacept (USAN/INN)
D03441	Certolizumab pegol (genetical recombination) (JAN)
D04358	Golimumab (genetical recombination) (JAN)
D04690	Lenercept (USAN/INN)
D05393	Pegsunercept (USAN)
D06634	Relacatib (USAN/INN)
D08866	Baminercept (USAN/INN)
D08955	Odanacatib (JAN/USAN)
D09704	Atacicept (USAN/INN)
D09967	Secukinumab (USAN/INN)

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]
100507709	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100507714	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
100509457	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
101060835	HLA class II histocompatibility antigen; K06752 major histocompatibility complex, class II [KO:K06752]
3683	ITGAL; integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1 [KO:K05718]
3689	ITGB2; integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) [KO:K06464]
3383	ICAM1; intercellular adhesion molecule 1 [KO:K06490]
3600	IL15; interleukin 15 [KO:K05433]
8741	TNFSF13; tumor necrosis factor (ligand) superfamily, member 13 [KO:K05475]
10673	TNFSF13B; tumor necrosis factor (ligand) superfamily, member 13b [KO:K05476]
4050	LTB; lymphotoxin beta (TNF superfamily, member 3) [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 (interferon, beta 2) [KO:K05405]
3589	IL11; interleukin 11 [KO:K05417]
3606	IL18; interleukin 18 (interferon-gamma-inducing factor) [KO:K05482]
7097	TLR2; toll-like receptor 2 [KO:K10159]
7099	TLR4; toll-like receptor 4 [KO:K10160]
3725	JUN; jun proto-oncogene [KO:K04448]
2353	FOS; FBJ murine osteosarcoma viral oncogene homolog [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, alpha subunit p19 [KO:K05426]
3605	IL17A; interleukin 17A [KO:K05489]
1435	CSF1; colony stimulating factor 1 (macrophage) [KO:K05453]
8600	TNFSF11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
8792	TNFRSF11A; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
523	ATP6V1A; ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A [KO:K02145] [EC:3.6.3.14]
525	ATP6V1B1; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 [KO:K02147] [EC:3.6.3.14]
526	ATP6V1B2; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B2 [KO:K02147] [EC:3.6.3.14]
245973	ATP6V1C2; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C2 [KO:K02148] [EC:3.6.3.14]
528	ATP6V1C1; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C1 [KO:K02148] [EC:3.6.3.14]
51382	ATP6V1D; ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D [KO:K02149] [EC:3.6.3.14]
90423	ATP6V1E2; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E2 [KO:K02150] [EC:3.6.3.14]
529	ATP6V1E1; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E1 [KO:K02150] [EC:3.6.3.14]
9296	ATP6V1F; ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F [KO:K02151] [EC:3.6.3.14]
9550	ATP6V1G1; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 [KO:K02152] [EC:3.6.3.14]
127124	ATP6V1G3; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G3 [KO:K02152] [EC:3.6.3.14]
534	ATP6V1G2; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2 [KO:K02152] [EC:3.6.3.14]
8992	ATP6V0E1; ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e1 [KO:K02153] [EC:3.6.3.14]
155066	ATP6V0E2; ATPase, H+ transporting V0 subunit e2 [KO:K02153] [EC:3.6.3.14]
10312	TCIRG1; T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3 [KO:K02154] [EC:3.6.3.14]
23545	ATP6V0A2; ATPase, H+ transporting, lysosomal V0 subunit a2 [KO:K02154] [EC:3.6.3.14]
50617	ATP6V0A4; ATPase, H+ transporting, lysosomal V0 subunit a4 [KO:K02154] [EC:3.6.3.14]
535	ATP6V0A1; ATPase, H+ transporting, lysosomal V0 subunit a1 [KO:K02154] [EC:3.6.3.14]
9114	ATP6V0D1; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d1 [KO:K02146] [EC:3.6.3.14]
245972	ATP6V0D2; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2 [KO:K02146] [EC:3.6.3.14]
51606	ATP6V1H; ATPase, H+ transporting, lysosomal 50/57kDa, V1 subunit H [KO:K02144] [EC:3.6.3.14]
537	ATP6AP1; ATPase, H+ transporting, lysosomal accessory protein 1 [KO:K03662] [EC:3.6.3.14]
527	ATP6V0C; ATPase, H+ transporting, lysosomal 16kDa, V0 subunit c [KO:K02155] [EC:3.6.3.14]
533	ATP6V0B; ATPase, H+ transporting, lysosomal 21kDa, V0 subunit b [KO:K03661] [EC:3.6.3.14]
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 (interstitial collagenase) [KO:K01388] [EC:3.4.24.7]
4314	MMP3; matrix metallopeptidase 3 (stromelysin 1, progelatinase) [KO:K01394] [EC:3.4.24.17]
1514	CTSL1; cathepsin L1 [KO:K01365] [EC:3.4.22.15]
1437	CSF2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
6352	CCL5; chemokine (C-C motif) ligand 5 [KO:K12499]
6347	CCL2; chemokine (C-C motif) ligand 2 [KO:K14624]
6348	CCL3; chemokine (C-C motif) ligand 3 [KO:K05408]
6349	CCL3L1; chemokine (C-C motif) ligand 3-like 1 [KO:K05408]
414062	CCL3L3; chemokine (C-C motif) ligand 3-like 3 [KO:K05408]
101060267	c-C motif chemokine 3-like; K05408 C-C motif chemokine 3 [KO:K05408]
6364	CCL20; chemokine (C-C motif) ligand 20 [KO:K14625]
6374	CXCL5; chemokine (C-X-C motif) ligand 5 [KO:K05506]
6372	CXCL6; chemokine (C-X-C motif) ligand 6 [KO:K05506]
3576	IL8; interleukin 8 [KO:K10030]
6387	CXCL12; chemokine (C-X-C motif) ligand 12 [KO:K10031]
7422	VEGFA; vascular endothelial growth factor A [KO:K05448]
2321	FLT1; fms-related tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
284	ANGPT1; angiopoietin 1 [KO:K05465]
7010	TEK; TEK tyrosine kinase, endothelial [KO:K05121] [EC:2.7.10.1]
3458	IFNG; interferon, gamma [KO:K04687]
2919	CXCL1; chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) [KO:K05505]

Compound

C00080	H+
C00584	Prostaglandin E2
C05443	Vitamin D3
C16051	Parathyroid hormone

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)

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)

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)

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)

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)

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)

Reference

PMID:9627005

Authors

Koch AE

Title

Review: angiogenesis: implications for rheumatoid arthritis.

Journal

Arthritis Rheum 41:951-62 (1998)

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)

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)

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)

Reference

PMID:19184540

Authors

Mensah KA, Li J, Schwarz EM

Title

The emerging field of osteoimmunology.

Journal

Immunol Res (2009)

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)

Reference

PMID:20392226

Authors

Takayanagi H

Title

New immune connections in osteoclast formation.

Journal

Ann N Y Acad Sci 1192:117-23 (2010)

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)

Reference

PMID:19455385

Authors

Nakashima T, Takayanagi H

Title

Osteoclasts and the immune system.

Journal

J Bone Miner Metab 27:519-29 (2009)

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)

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)

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)

KO pathway

ko05323

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Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (2)   
   KEGG DISEASE (2)   
Drug (15)   
   KEGG DRUG (15)   
Genome (1)   
   KEGG GENOME (1)   
Gene (94)   
   KEGG GENES (94)   
All databases (115)   

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