Malondialdehyde-acetaldehyde adducts and anti-malondialdehyde-acetaldehyde antibodies in rheumatoid arthritis

Geoffrey Milton Thiele, Michael J. Duryee, Daniel R Anderson, Lynell Warren Klassen, Stephen M. Mohring, Kathleen A. Young, Dathe Benissan-Messan, Harlan Sayles, Anand Dusad, Carlos D. Hunter, Jeremy Sokolove, William H. Robinson, James Robert O'Dell, Anthony P. Nicholas, Dean J. Tuma, Ted R Mikuls

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Objective Malondialdehyde-acetaldehyde (MAA) adducts are a product of oxidative stress associated with tolerance loss in several disease states. This study was undertaken to investigate the presence of MAA adducts and circulating anti-MAA antibodies in patients with rheumatoid arthritis (RA). Methods Synovial tissue from patients with RA and patients with osteoarthritis (OA) were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA patients (n = 1,720) and healthy controls (n = 80) by enzyme-linked immunosorbent assay. Antigen-specific anti-citrullinated protein antibodies (ACPAs) were measured in RA patients using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of RA patients (n = 80) and matched healthy controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA positivity, were examined in all RA patients. Results Expression of MAA adducts was increased in RA synovial tissue compared to OA synovial tissue, and colocalization with citrullinated proteins was found. Increased levels of anti-MAA antibody isotypes were observed in RA patients compared to controls (P < 0.001). Among RA patients, anti-MAA antibody isotypes were associated with seropositivity for ACPAs and rheumatoid factor (P < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a greater number of positive antigen-specific ACPA analytes (expressed at high titer) (P < 0.001) and a higher ACPA score (P < 0.001), independent of other covariates. Conclusion MAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPAs. These results support speculation that MAA formation may be a cofactor that drives tolerance loss, resulting in the autoimmune responses characteristic of RA.

Original languageEnglish (US)
Pages (from-to)645-655
Number of pages11
JournalArthritis and Rheumatology
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2015

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

Thiele, G. M., Duryee, M. J., Anderson, D. R., Klassen, L. W., Mohring, S. M., Young, K. A., Benissan-Messan, D., Sayles, H., Dusad, A., Hunter, C. D., Sokolove, J., Robinson, W. H., O'Dell, J. R., Nicholas, A. P., Tuma, D. J., & Mikuls, T. R. (2015). Malondialdehyde-acetaldehyde adducts and anti-malondialdehyde-acetaldehyde antibodies in rheumatoid arthritis. Arthritis and Rheumatology, 67(3), 645-655. https://doi.org/10.1002/art.38969