Abstract
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.
Highlights
It has long been known that there is a connection between seropositive rheumatoid arthritis (RA) and smoking
Vessey and colleagues described an association between hospitalization due to RA and cigarette smoking, which was an unexpected finding of their gynecological study [1]
The role of EBV in the RA pathogenesis is supported by several other data: the anti-EBV titer is elevated in RA patients; certain EBV antigens share similarities with synovial self-autoantigens providing the possibility of viral cross-reactivity; the gp110 glycoprotein in EBV contains a copy of shared epitope (SE); cell-mediated responses against EBV proteins
Summary
It has long been known that there is a connection between seropositive rheumatoid arthritis (RA) and smoking. Recent data suggest that cigarette smoking establishes a higher risk for anti-citrullinated protein antibody (ACPA)-positive RA. A nationwide case–control study involving known and recently diagnosed RA patients conducted in Denmark has proved strong gene–environment effects: there was an increased risk for anti-CCP-positive RA in heavy smokers with homozygote SE alleles [67]. A case-only analysis of three North American RA cohorts – RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) family collection, from the National Inception Cohort of Rheumatoid Arthritis Patients, and from the Study of New Onset Rheumatoid Arthritis (SONORA) – has shown an association between smoking and anti-CCP in To conclude, these data suggest there may be an association between smoking, SE alleles and ACPA-positive RA.
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