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.
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.
Authors: Michael J Duryee; Lynell W Klassen; Thomas L Freeman; Monte S Willis; Dean J Tuma; Geoffrey M Thiele Journal: Alcohol Clin Exp Res Date: 2004-12 Impact factor: 3.455
Authors: Michael J Duryee; Lynell W Klassen; Courtney S Schaffert; Dean J Tuma; Carlos D Hunter; Robert P Garvin; Daniel R Anderson; Geoffrey M Thiele Journal: Free Radic Biol Med Date: 2010-08-06 Impact factor: 7.376
Authors: Kristine A Kuhn; Liudmila Kulik; Beren Tomooka; Kristin J Braschler; William P Arend; William H Robinson; V Michael Holers Journal: J Clin Invest Date: 2006-04 Impact factor: 14.808
Authors: Michael J Duryee; Lynell W Klassen; Thomas L Freeman; Monte S Willis; Dean J Tuma; Geoffrey M Thiele Journal: Biochem Pharmacol Date: 2003-09-15 Impact factor: 5.858
Authors: Monte S Willis; Lynell W Klassen; Deborah L Carlson; Chad F Brouse; Geoffrey M Thiele Journal: Int Immunopharmacol Date: 2004-07 Impact factor: 4.932
Authors: Catriona A Wagner; Jeremy Sokolove; Lauren J Lahey; Camilla Bengtsson; Saedis Saevarsdottir; Lars Alfredsson; Michelle Delanoy; Tamsin M Lindstrom; Roger P Walker; Reuven Bromberg; Piyanka E Chandra; Steven R Binder; Lars Klareskog; William H Robinson Journal: Ann Rheum Dis Date: 2013-12-02 Impact factor: 19.103
Authors: Ted R Mikuls; Michael J Duryee; Rafid Rahman; Daniel R Anderson; Harlan R Sayles; Andrew Hollins; Kaleb Michaud; Frederick Wolfe; Geoffrey E Thiele; Jeremy Sokolove; William H Robinson; Nithya Lingampalli; Anthony P Nicholas; Geoffrey A Talmon; Kaihong Su; Matthew C Zimmerman; Lynell W Klassen; Geoffrey M Thiele Journal: Rheumatology (Oxford) Date: 2017-10-01 Impact factor: 7.580
Authors: Ted R Mikuls; Jess Edison; Elizabeth Meeshaw; Harlan Sayles; Bryant R England; Michael J Duryee; Carlos D Hunter; Lindsay B Kelmenson; Laura Kay Moss; Marie L Feser; Brandie Wagner; Mark C Parish; Kevin D Deane; Geoffrey M Thiele Journal: Arthritis Rheumatol Date: 2020-10-15 Impact factor: 10.995
Authors: Michael J Duryee; Benjamin M Wiese; Jordan R Bowman; Jared D Vanlandingham; Lynell W Klassen; Geoffrey E Thiele; Carlos D Hunter; Daniel R Anderson; Ted R Mikuls; Geoffrey M Thiele Journal: Am J Physiol Gastrointest Liver Physiol Date: 2017-12-28 Impact factor: 4.052