Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Bryant R. England, Michael J. Duryee, Punyasha Roul, Tina D. Mahajan, Namrata Singh, Jill A. Poole, Dana P. Ascherman, Liron Caplan, M. Kristen Demoruelle, Kevin D. Deane, Lynell W. Klassen, Geoffrey M. Thiele, Ted R. Mikuls

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Objective: To compare serum anti–malondialdehyde–acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) to those found in controls. Methods: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19–4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. Conclusion: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.

Original languageEnglish (US)
Pages (from-to)1483-1493
Number of pages11
JournalArthritis and Rheumatology
Issue number9
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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