{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:52:35Z","timestamp":1789602755658,"version":"build-2803163510"},"reference-count":10,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T00:00:00Z","timestamp":1625356800000},"content-version":"am","delay-in-days":262,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006379","name":"Office of Research and Development","doi-asserted-by":"publisher","award":["BX004790"],"award-info":[{"award-number":["BX004790"]}],"id":[{"id":"10.13039\/100006379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001082"],"award-info":[{"award-number":["UL1 TR001082"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54GM115458"],"award-info":[{"award-number":["U54GM115458"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["PR180230"],"award-info":[{"award-number":["PR180230"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine serum autoantibodies to malondialdehyde\u2013acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Concentrations of anti\u2010MAA antibody isotypes, anti\u2013cyclic citrullinated peptide 2 (anti\u2013CCP\u20102), and IgM rheumatoid factor (IgM\u2010RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed models for each antibody and\/or isotype. Associations between prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Concentrations of IgG (log<jats:sub>2<\/jats:sub> difference 0.34) and IgA (log<jats:sub>2<\/jats:sub> difference 0.43) anti\u2010MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively (<jats:italic>P<\/jats:italic> &lt; 0.05 for both). There was no evidence of case\u2013control divergence for IgM anti\u2010MAA antibody concentration. Anti\u2013CCP\u20102 and IgM\u2010RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti\u2010MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti\u2013CCP\u20102 antibody and RF concentrations prior to diagnosis (\u03b2 = 0.22\u20130.27 for IgM\u2010RF; \u03b2 = 0.44\u20130.93 for anti\u2013CCP\u20102) (<jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IgG and IgA anti\u2010MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti\u2013CCP\u20102 or RF. These findings suggest that MAA formation and anti\u2010MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41424","type":"journal-article","created":{"date-parts":[[2020,7,4]],"date-time":"2020-07-04T09:29:11Z","timestamp":1593854951000},"page":"2025-2029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Autoantibodies to Malondialdehyde\u2013Acetaldehyde Are Detected Prior to Rheumatoid Arthritis Diagnosis and After Other Disease Specific Autoantibodies"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-2272","authenticated-orcid":false,"given":"Ted R.","family":"Mikuls","sequence":"first","affiliation":[{"name":"University of Nebraska Medical Center, Omaha and VA Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jess","family":"Edison","sequence":"additional","affiliation":[{"name":"Walter Reed National Military Medical Center  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Meeshaw","sequence":"additional","affiliation":[{"name":"Walter Reed National Military Medical Center  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan","family":"Sayles","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center  Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-3588","authenticated-orcid":false,"given":"Bryant R.","family":"England","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha and VA Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Duryee","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center  Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos D.","family":"Hunter","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center  Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay B.","family":"Kelmenson","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kay Moss","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"Feser","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandie","family":"Wagner","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Parish","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-4861","authenticated-orcid":false,"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"University of Colorado  Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey M.","family":"Thiele","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha and VA Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.01.022"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40900"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex212"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38969"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.7205\/MILMED-D-14-00739"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41091"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21606-5"},{"key":"e_1_2_6_10_1","article-title":"Immunogenic and inflammatory responses to citrullinated proteins are enhanced following modificaiton with malondialdehyde\u2010acetaldehyde adducts","volume":"83106433","author":"Thiele GM","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.024"}],"container-title":["Arthritis &amp; 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