Authors: Ted R. Mikuls, Jess Edison, Elizabeth Meeshaw, Harlan Sayles, Bryant R. England, Michael J. Duryee, Carlos D. Hunter, Lindsay B. Kelmenson, Laura Kay Moss, Marie L. Feser, Brandie Wagner, Mark C. Parish, Kevin D. Deane, Geoffrey M. Thiele
Published: 2020-07-04
DOI: 10.1002/art.41424
Source: Full article
ObjectiveTo examine serum autoantibodies to malondialdehyde–acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis.MethodsConcentrations of anti‐MAA antibody isotypes, anti–cyclic citrullinated peptide 2 (anti–CCP‐2), and IgM rheumatoid factor (IgM‐RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). 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 prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models.ResultsConcentrations of IgG (log2 difference 0.34) and IgA (log2 difference 0.43) anti‐MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively (P < 0.05 for both). There was no evidence of case–control divergence for IgM anti‐MAA antibody concentration. Anti–CCP‐2 and IgM‐RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti‐MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti–CCP‐2 antibody and RF concentrations prior to diagnosis (β = 0.22–0.27 for IgM‐RF; β = 0.44–0.93 for anti–CCP‐2) (P < 0.001).ConclusionIgG and IgA anti‐MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti–CCP‐2 or RF. These findings suggest that MAA formation and anti‐MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.