Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA.

METHOD: From two population-based case-control studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma cases with a validated RA diagnosis (n = 50), to whom we matched study participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and neither RA nor lymphoma (n = 233). Lymphomas were classified according to the WHO classification. Blood samples were analysed for immunoglobulin G (IgG), IgM, and IgA isotypes and IgG1-4 subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression.

RESULTS: We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA.

CONCLUSION: In this study, neither anti-CCP antibodies (IgG, IgG1-4 , IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA.