Share Epitope, Citrullinated Cyclic Peptide Antibodies and Smoking in Brazilian Rheumatoid Arthritis Patients

Abstract

The events involved in the pathogenesis of rheumatoid arthritis (RA) still remain unclear, but certainly the etiology is multifactorial. Shared epitope (SE) of HLADRbeta1 is the most important genetic risk factor. Environmental risk factors are less understood. Smoking is a candidate, associated with the rising of citrullinated cyclic peptide antibodies (anti-CCP). Anti-CCP antibodies are highly specific for RA. In this study, we investigated whether the association between anti-CCP production and smoking was influenced by carriage of SE in a highly miscegenated population of patients with RA. One hundred Brazilian patients were inquired about cigarette smoking. For all of them, DNA for HLA typing and serum to anti-CCP antibodies quantification were obtained. Forty-two were smokers and 58 were nonsmokers. The SE was present in 61 patients and the anti-CCP was positive in 71 patients. We found that, among smokers, 25 were SE-positive, 22 presented with anti-CCP and 3 without anti-CCP, and 17 were SE-negative, 9 presented with anti-CCP and 8 without anti-CCP (OR 6.5, 95% CI 1.40 to 30.20). These results suggest that environmental factors contribute to the raising of anti-CCP in individuals with HLA background to RA, smoking being a strong candidate.

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

“…As reported in more homogeneously Caucasian populations5-8, we showed that SE alleles and tobacco exposure are related to anti-CCP antibodies in RA patients. Several previous studies observed these same relationships in Brazilian RA patients 34,35…”

A majority of Brazilian patients with rheumatoid arthritis HLA-DRB1 alleles carry both the HLA-DRB1 shared epitope and anti-citrunillated peptide antibodies

“…Environmental risk factors are less understood. Smoking is a candidate, associated with increased citrullinated cyclic peptide antibodies (30)(31)(32). In this study, we investigated the associations between HLA class II alleles and RA and the protective effects of the DERAA-encoding HLA-DRB1 alleles on RA susceptibility.…”

Collagen induced arthritis (CIA) in mice features regulatory transcriptional network connecting major histocompatibility complex (MHC H2) with autoantigen genes in the thymus

“…in association to genetic background of MHC alleles. In RA, complex environmental and genetic factors are believed to contribute to their development (Oliveira et al 2008). Human leukocyte antigen genes class II region on chromosome 6 (HLA-DRB1 alleles *0401, *0404, *0405, *0408, *0101, *0102, *1001 and *1402) have been strongly associated with susceptibility to the disease, according to the population studied (du Montcel et al 2005).…”