Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles.

Abstract:

OBJECTIVES:To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis. METHODS:From incident cases of arthritis (n = 1305), patients who did not fulfil any classification criteria (undifferentiated arthritis (n = 486)) and those who fulfilled the American College of Rheumatology criteria for rheumatoid arthritis (n = 407) were identified. IgM rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) antibodies, and HLA-DRB1 alleles were determined. RESULTS:In rheumatoid arthritis, an interaction was found between tobacco exposure and shared epitope for the presence of anti-CCP antibodies, as the odds ratio for anti-CCP antibodies in patients having both tobacco exposure (TE) and shared epitope (SE) was higher than the summed odds ratios of patients having only tobacco exposure or shared epitope (odds ratios: TE+/SE-, 1.07; TE-/SE+, 2.49; and TE+/SE+, 5.27-all relative to TE-/SE-). A similar effect was found for RF, but stratification showed that the interaction primarily associated with the anti-CCP antibody response. In patients with undifferentiated arthritis at two weeks, or with persistent undifferentiated arthritis after one year, no interaction between tobacco exposure and shared epitope was observed for the presence of autoantibodies. CONCLUSIONS:Tobacco exposure increases the risk factor for anti-CCP antibodies only in shared epitope positive patients with rheumatoid arthritis. The gene-environment interaction between smoking and shared epitope leading to autoantibodies is specific for rheumatoid arthritis and is not observed in undifferentiated arthritis.

journal_name

Ann Rheum Dis

authors

Linn-Rasker SP,van der Helm-van Mil AH,van Gaalen FA,Kloppenburg M,de Vries RR,le Cessie S,Breedveld FC,Toes RE,Huizinga TW

doi

10.1136/ard.2005.041079

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

366-71

issue

3

eissn

0003-4967

issn

1468-2060

pii

ard.2005.041079

journal_volume

65

pub_type

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