5 Questions About Anti-MAA Antibodies in RA-Associated Interstitial Lung Disease

Individuals with rheumatoid arthritis (RA) have an increased risk of premature mortality. Those with RA-associated interstitial lung disease (RA-ILD) have an even greater risk, with a median survival of 3 years after diagnosis.¹

Bryant England, MD, an assistant professor of internal medicine at the VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center in Omaha, Nebraska, and colleagues compared serum anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies and MAA expression in lung tissues of more than 1823 individuals with RA alone, RA‐ILD, or RA with chronic obstructive pulmonary disease (COPD).²

The results showed that anti-MAA antibodies and MAA expression may have an important role in RA-ILD pathogenesis and could be serum biomarkers for the identification of RA-ILD.

Rheumatology Consultant caught up with Dr England about the research.

Rheumatology Consultant: What is known about the relationship between RA and ILD?

Bryant England: ILD complicates the disease course in some individuals with RA and leads to premature mortality. A substantial proportion of the premature mortality among individuals with RA is a result of ILD.

RHEUM CON: What prompted you to conduct your study?

BE: Our group has been studying the role of MAA-modified proteins and their immune responses in RA for some time. There is literature from in vitro and animal studies that demonstrate the role of MAA in lung inflammatory responses and wound healing. The lungs have great exposure to oxidative stress. Since MAA is generated from oxidative stress, we hypothesized that MAA may be an important molecule that links oxidative stress or epithelial insult to inflammatory and fibrotic process, which could result in RA-ILD.

RHEUM CON: Were you surprised that serum anti‐MAA antibody concentrations were higher among individuals with RA‐ILD compared with individuals with RA alone or RA and COPD?

BE: There are a limited number of studies evaluating biomarkers in RA-ILD compared to other chronic lung diseases. We wanted to test whether anti-MAA antibodies were unique to RA-ILD or were also found in COPD. We expected the antibodies to be unique to RA-ILD given the links between epithelial damage and oxidative stress that accompany ILD and pulmonary fibrosis. This specificity of anti-MAA antibodies to RA-ILD makes it attractive to be integrated into a screening approach for RA-ILD.

RHEUM CON: What are the clinical implications of your study?

BE: MAA antibodies may have clinical utility for being integrated into part of an ILD screening protocol for individuals with RA. Furthermore, the tissue analyses showed higher prevalence of MAA in RA-ILD; its colocalization with citrullinated peptides and extracellular matrix proteins suggests there may be a pathogenic role for MAA in RA-ILD. Further exploration of this may lead to the identification of novel targets for therapeutics.

RHEUM CON: What are the next steps of your research?

BE: We need to evaluate whether anti-MAA antibody responses in RA-ILD are unique to the antigen that is MAA-adducted. Furthermore, we want to test the clinical utility of the antibodies as biomarkers for RA-ILD, as well as continue to elucidate the role of MAA and immune responses to MAA in linking oxidative stress, autoimmunity, inflammation, and fibrosis in RA-ILD pathogenesis.

References:

1. Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population‐based study. Arthritis Rheum. 2010;62(6):1583-1591. doi:10.1002/art.27405.
2. England BR, Duryee MJ, Roul P, et al. Malondialdehyde-acetaldehyde adducts and antibody responses in rheumatoid arthritis-associated interstitial lung disease [published online April 1, 2019]. Arthritis Rheumatol. doi:10.1002/art.40900.

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