Antibodies to Malondialdehyde‐Acetaldehyde Adduct Are Associated With Prevalent and Incident Rheumatoid Arthritis–Associated Interstitial Lung Disease in US Veterans

Abstract

ObjectiveTo determine the associations of protein‐specific anti‐malondialdehyde acetaldehyde (MAA) antibodies with prevalent and incident rheumatoid arthritis‐interstitial lung disease (RA‐ILD).MethodsWithin a multicenter, prospective cohort of U.S. Veterans with RA, RA‐ILD was validated by medical record review of clinical diagnoses, chest imaging, and pathology. Serum antibodies to MAA‐albumin, MAA‐collagen, MAA‐fibrinogen, and MAA‐vimentin (IgA, IgM, and IgG) were measured by a standardized ELISA. Associations of anti‐MAA antibodies with prevalent and incident RA‐ILD were assessed using multivariable regression models adjusting for established RA‐ILD risk factors.ResultsAmong 2,739 RA participants (88% male, mean age 64 years), there were 114 prevalent and 136 incident RA‐ILD cases (average time to diagnosis: 6.6 years). Higher IgM anti‐MAA‐collagen (per 1 SD: aOR 1.28 [1.02‐1.61]), IgA anti‐MAA‐fibrinogen (aOR 1.48 [1.14‐1.92]), and IgA (aOR 1.78 [1.34‐2.37]) and IgG (aOR 1.48 [1.14‐1.92]) anti‐MAA‐vimentin antibodies were associated with prevalent RA‐ILD. In incident analyses, higher IgA (per 1 SD: aHR 1.40 [1.11‐1.76]) and IgM (aHR 1.29 [1.04‐1.60]) anti‐MAA‐albumin antibody concentrations were associated with increased ILD risk. Participants with IgA (aHR 2.13 [1.16‐3.90]) or IgM (aHR 1.98 [1.08‐3.64]) anti‐MAA‐albumin antibody concentrations in the highest quartile had an approximate 2‐fold increased risk of incident RA‐ILD. Across all isotypes, anti‐MAA‐fibrinogen, ‐collagen, and ‐vimentin antibodies were not significantly associated with incident RA‐ILD.ConclusionsProtein‐specific anti‐MAA antibodies to collagen, fibrinogen, and vimentin were associated with prevalent RA‐ILD. IgA and IgM anti‐MAA‐albumin antibodies were associated with a higher risk of incident RA‐ILD. These findings suggest that MAA‐modifications and resultant immune responses may contribute to RA‐ILD pathogenesis.