Anti-malondialdehyde-acetaldehyde adducts (MAA) antibodies and MAA expression in lung tissues of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) likely play an important role in RA-ILD pathogenesis, and anti-MAA antibodies may function well as serum biomarkers in the identification of this disease manifestation, according to a study published in Arthritis and Rheumatology.
Patients with RA already face premature mortality and RA-ILD is a major determinant of worse long-term outcomes, with a median survival as short as 3 years after diagnosis. For the current study, researchers compared serum anti-MAA antibodies and MAA expression in lung tissues of patients from 13 sites fulfilling the 1987 American College of Rheumatology criteria by selecting participants from the Veterans Affairs Rheumatoid Arthritis Registry, a multicenter prospective observational study of US veterans with RA. Multivariable logistic regression models were used to assess the association between anti-MAA antibodies (immunoglobulins A, M, and G [IgA, IgM, IgG]) and RA-ILD status by combining RA alone with RA+chronic obstructive pulmonary disease (COPD) for a comparator group, as unadjusted comparisons found no significant differences in concentrations of anti-MAA antibodies between these groups. Lung tissues from RA-ILD patients, and other patients with ILD, emphysema, and controls were stained for MAA, macrophages (CD68), citrulline, B cells (CD19/CD27), T cells (CD3), and extracellular matrix proteins (fibronectin, vimentin, type-II collagen). Lung tissue expression and MAA co-localization were quantified and compared.
Among the total 1823 participants with RA, 90 had RA-ILD. Higher serum concentrations of IgM and IgA anti-MAA antibodies were seen in RA-ILD vs RA+COPD or RA alone (P =.005). After adjustment for covariates, the highest quartiles of IgM (odds ratio [OR] 2.23; 95% CI, 1.19-4.15) and IgA (OR 2.09; 95% CI, 1.11-3.90) anti-MAA antibody were significantly associated with RA-ILD. MAA expression in lung tissue was greater in RA-ILD than all other groups (P <.001). The RA-ILD group also showed the greatest degree of MAA co-localized with CD19+ B cells (r =0.78), citrulline (r =0.79), and extracellular matrix proteins (type-II collagen [r =0.72] and vimentin [r =0.77]).
Study investigators concluded that, “These findings suggest that MAA immune responses could play an important role in the pathogenesis of RA-ILD and anti-MAA antibodies may be promising serum biomarkers in the identification of this extra-articular disease manifestation.”
England BR, Duryee MJ, Roul P, et al. Malondialdehyde-acetaldehyde adducts and antibody responses in rheumatoid arthritis-interstitial lung disease [published online April 1, 2019]. Arthritis Rheumatol. doi: 10.1002/art.40900