{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:50:15Z","timestamp":1791838215937,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T00:00:00Z","timestamp":1424822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Medicine"},{"name":"Nebraska Arthritis Outcomes Research Center"},{"name":"VA Merit Award"},{"name":"Umbach Professorship in Arthritis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Malondialdehyde\u2010acetaldehyde (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\u2010MAA antibodies in patients with rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial tissue from patients with RA and patients with osteoarthritis (OA) were examined for the presence of MAA\u2010modified and citrullinated proteins. Anti\u2010MAA antibody isotypes were measured in RA patients (n = 1,720) and healthy controls (n = 80) by enzyme\u2010linked immunosorbent assay. Antigen\u2010specific anti\u2013citrullinated protein antibodies (ACPAs) were measured in RA patients using a multiplex antigen array. Anti\u2010MAA isotype concentrations were compared in a subset of RA patients (n = 80) and matched healthy controls (n = 80). Associations of anti\u2010MAA antibody isotypes with disease characteristics, including ACPA positivity, were examined in all RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010MAA antibody isotypes were observed in RA patients compared to controls (<jats:italic>P<\/jats:italic> &lt; 0.001). Among RA patients, anti\u2010MAA antibody isotypes were associated with seropositivity for ACPAs and rheumatoid factor (<jats:italic>P<\/jats:italic> &lt; 0.001) in addition to select measures of disease activity. Higher anti\u2010MAA antibody concentrations were associated with a greater number of positive antigen\u2010specific ACPA analytes (expressed at high titer) (<jats:italic>P<\/jats:italic> &lt; 0.001) and a higher ACPA score (<jats:italic>P<\/jats:italic> &lt; 0.001), independent of other covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38969","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T15:23:36Z","timestamp":1416583416000},"page":"645-655","source":"Crossref","is-referenced-by-count":148,"title":["Malondialdehyde\u2010Acetaldehyde Adducts and Anti\u2013Malondialdehyde\u2010Acetaldehyde Antibodies in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Geoffrey M.","family":"Thiele","sequence":"first","affiliation":[{"name":"VA Nebraska\u2013Western Iowa Health Care System, Omaha, Nebraska, and University of Nebraska Medical Center Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Duryee","sequence":"additional","affiliation":[{"name":"VA Nebraska\u2013Western Iowa Health Care System, Omaha, Nebraska, and 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