Background The pathophysiology of rheumatoid arthritis (RA) is currently viewed as a process that starts with a pathologic activation of the immune system that eventually leads to the clinical manifestation of the disease. Systemic autoimmunity has been defined as one of the specific phases preceding the development of RA.(1) Different risk factors may be relevant for each specific phase in RA disease development.
Objectives To analyse putative environmental, genetic and demographic risk factors associated with the development of systemic autoimmunity associated with RA in individuals genetically at risk.
Methods This is a prospective cohort study of individuals genetically at risk of developing RA, namely first degree relatives (FDRs) of patients with known active RA. Only individuals without clinical evidence of RA were enrolled, and then followed-up yearly to detect the development of active arthritis. We included in this analysis only individuals with available anti-CCP status (anti-CCP 2.0 or anti-CCP 3.1). We pooled individuals from two separate cohorts, one from Switzerland (N=682) and one from France (N=148). We used logistic regression to analyse univariate and multivariate associations between a positive anti-CCP status and putative risk factors.
Results A total of 830 FDRs of RA patients are presented, of which 41 (5%) were anti-CCP positive. FDRs had a mean age of 46 years, 79% female, 61% shared epitope positive, and 24% had a history of at least one episode of swollen joint, either at inclusion or during follow-up.
In univariate analysis, a positive anti-CCP status was significantly associated with heavy tobacco smoke (>10 pack-years, Odds Ratio (OR): 2.8, p=0.02), loss of teeth (OR: 1.07, p=0.001), the presence of a swollen (OR: 2.5, p=0.04) or a tender joint (OR: 2.1, p=0.03). In multivariate adjusted analysis, only loss of teeth (OR: 1.06, p=0.005), heavy tobacco smoke (OR: 2.6, p=0.039) and the history of a swollen joints (OR: 1.16, p=0.002) were independently associated with anti-CCP positivity. Furthermore, male sex trended to be protective (OR: 0.39, p=0.089) and the effect of obesity on anti-CCP development tended to differ by sex. In males obesity was associated with an increased risk, while in women obesity was associated with a decreased risk (OR: 4.86 vs. OR: 0.18, p=0.075). No association between anti-CCP and the presence of the shared epitope, alcohol consumption or various joint symptoms was found, which may be explained by limited statistical power.
Conclusions In individuals genetically at risk for RA, the development of anti-CCP antibodies was associated with tooth loss, tobacco smoke and the occurrence of a swollen joint. Taken together, these results suggest similar risk factors for the production of anti-CCP antibodies and the development of classifiable RA, suggesting that the occurrence of anti-CCP antibodies is a valid intermediate marker of RA development.
Gerlag DM et al. Ann Rheum Dis 2012.
Acknowledgements All investigators and participants within the “SCREEN-RA” and the “Campagne des 100'000” studies.
Disclosure of Interest : None declared
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