The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis. A study on disease discordant twin pairs

ObjectiveTo assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.MethodsA co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins. Outcome measures: The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking.ResultsThe probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4–92.4), 16.7 (0.6–58.4), 30.0 (7.3–60.6), 42.1 (14.5–71.1) in MZ twins and 25.0 (10.3–44.4), 0.0 (0.0–27.7), 10.5 (1.4–31.5) and 22.2 (6.8–45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5–236.5) 9 (1.3–394.5) 272 (3.5–593.2) and 10 (1.4–434.0) in MZ twin pairs and 17 (4.4–146.1) 20 (3.2–828.0) 33 (5.5–1342.4) and 577 (7.4–1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3–213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction.ConclusionThere is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.

► There is a higher concordance of antibodies in MZ than DZ RA discordant twin pairs. ► Environmental factors may trigger the expression of antibodies in healthy co-twins. ► The genetic susceptibility for ACPA goes beyond the shared epitope and PTPN22.