Autoantibodies to Malondialdehyde-Acetaldehyde Are Detected Prior to Rheumatoid Arthritis Diagnosis and After Other Disease Specific Autoantibodies.

OBJECTIVES To examine serum autoantibodies to malondialdehyde-acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis. METHODS Anti-MAA antibody isotypes, anti-CCP2, and RF-IgM were measured in pre- and post-RA diagnosis samples (n=214 cases, 210 controls). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed-models for each antibody and/or isotype. Associations between pre-diagnosis autoantibody concentrations in cases were examined using mixed effects linear regression models. RESULTS IgG (log2 difference 0.34) and IgA (log2 difference 0.43) anti-MAA antibody concentrations in cases diverged from controls 3.0 and 2.3 years, respectively, pre-RA diagnosis (p <0.05). There was no evidence of case-control divergence for IgM anti-MAA antibody. Anti-CCP2 and RF-IgM concentrations diverged between cases and controls beginning 17.6 and 7.2 years, respectively, prior to RA diagnosis. All three anti-MAA antibody isotypes were significantly associated with anti-CCP2 antibody and RF concentrations pre-diagnosis (β = 0.22-0.27 for RF-IgM; β = 0.44-0.93 for anti-CCP2; p <0.001). CONCLUSIONS IgG and IgA anti-MAA autoantibodies are elevated pre-RA diagnosis but appear later in the pre-clinical course than anti-CCP2 or RF. These results suggest that MAA formation and anti-MAA immune responses could have a role in the transition from subclinical autoimmunity to clinically apparent arthritis.