In RA, increased cytokine presence creates a chronic signalling loop through the JAK-STAT pathway, which may lead to overproduction of proinflammatory cytokines and activation of immune cells that can result in tissue destruction, systemic inflammation, and escalating cycles of autoimmunity.2-6
Inflammation
Blood vessel formation
Bone destruction
Autoimmunity6-8
Lymphocyte proliferation1 Differentiation of NK cells1,14
Pain and inflammation
Blood vessel and pannus formation
Bone and cartilage destruction
Autoimmunity
Systemic symptoms8-10
T cell differentiation and
homeostasis
Granulocyte production1,14
Inflammation
Synovial tissue remodelling
Autoimmunity8,11,12
Innate antiviral defence1
Autoimmunity13
Red blood cell production
Bone marrow production
Platelet production1
Inflammation
Synovial tissue remodelling
Autoimmunity8
Innate antiviral defence
Antitumour1
HCP, healthcare provider; JAK, Janus kinase; NK, natural killer; RA, rheumatoid arthritis; STAT, signal transducer and activator of transcription.
REFERENCES
1. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243. 2. Hodge JA, Kawabata TT, Krishnaswami S, et al. Clin Exp Rheumatol. 2016;34(2):318-328. 3. McInnes IB, Schett G. Nat Rev Immunol. 2007;7(6):429-442. 4. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 5. Schett G. Rheumatology (Oxford). 2018;57(suppl 2):ii43-ii50. 6. Dinesh P, Rasool M. J Cell Physiol. 2018;233(5):3918-3928. 7. Chen Z, Han Y, Gu Y, et al. J Immunol. 2013;190(12):5256-5266. 8. Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Nat Rev Rheumatol. 2016;12(1):25-36. 9. Srirangan S, Choy EH. Ther Adv Musculoskelet Dis. 2010;2(5):247-256. 10. Boettger MK, Leuchtweis J, Kümmel D, Gajda M, Bräuer R, Schaible HG. Arthritis Res Ther. 2010;12(4):R140. 11. Schurgers E, Billiau A, Matthys P. J Interferon Cytokine Res. 2011;31(12):917-926. 12. Aletaha D, Smolen JS. JAMA. 2018;320(13):1360-1372. 13. Lotfi N, Thome R, Rezaei N, et al. Front Immunol. 2019;10:1265. 14. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038. 15. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 16. Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. BioDrugs. 2019;33(1):15-32.
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