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. 2009;11(4):238.
doi: 10.1186/ar2751. Epub 2009 Aug 3.

Rheumatoid Arthritis and Smoking: Putting the Pieces Together

Free PMC article

Rheumatoid Arthritis and Smoking: Putting the Pieces Together

Zsuzsanna Baka et al. Arthritis Res Ther. .
Free PMC article


Besides atherosclerosis and lung cancer, smoking is considered to play a major role in the pathogenesis of autoimmune diseases. It has long been known that there is a connection between rheumatoid factor-positive rheumatoid arthritis and cigarette smoking. Recently, an important gene-environment interaction has been revealed; that is, carrying specific HLA-DRB1 alleles encoding the shared epitope and smoking establish a significant risk for anti-citrullinated protein antibody-positive rheumatoid arthritis. We summarize how smoking-related alteration of the cytokine balance, the increased risk of infections (the possibility of cross-reactivity) and modifications of autoantigens by citrullination may contribute to the development of rheumatoid arthritis.


Figure 1
Figure 1
Complex role of smoking in the pathogenesis of rheumatoid arthritis. ACPA, anti-citrullinated protein antibody; AP-1, activator protein-1; EBV, Epstein–Barr virus; HQ, hydroquinone; IRF-5, interferon regulatory factor 5; nACh, nicotinic acetylcholine; PAD, peptidyl arginine deiminase; PADI4, gene of peptidyl arginine deiminase type 4; PTPN22, protein tyrosine phosphatase nonreceptor 22; RA, rheumatoid arthritis; RF, rheumatoid factor; SE, shared epitope.

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