{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:47:51Z","timestamp":1791906471066,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,2]],"date-time":"2023-04-02T00:00:00Z","timestamp":1680393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The present study was undertaken to longitudinally evaluate titers of antibodies against \u03b2<jats:sub>2<\/jats:sub>\u2010glycoprotein I (anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI) and domain 1 (anti\u2010D1), to identify predictors of variations in anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI and anti\u2010D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with available blood samples from at least 4 time points (at baseline [year 1] and at years 2\u20134 of follow\u2010up) were included. Detection of anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI and anti\u2010D1 IgG antibodies was performed using chemiluminescence (BIO\u2010FLASH; INOVA Diagnostics).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 230 patients in the study cohort, anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers decreased significantly over time (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001 and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3\u2010fold and 1.4\u2010fold decreases in anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers, respectively. Incident vascular events were associated with 1.9\u2010fold and 2.1\u2010fold increases in anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers, respectively. Anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6\u2010fold decrease in anti\u2010D1 titers and a 2\u2010fold decrease in anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval [95% CI] 0.62\u201359.3) and 9.4 (95% CI 1.1\u201380.2), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with HCQ and incident vascular events in aPL\u2010positive patients predicted significant anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titer fluctuations over time. Both anti\u2010D1 and anti\u2010\u03b2<jats:sub>2<\/jats:sub>GPI titers decreased around the time of thrombosis, with potential clinical relevance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42459","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T03:36:34Z","timestamp":1674790594000},"page":"984-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Fluctuation of Anti\u2013Domain 1 and Anti\u2013<scp>\u03b2<sub>2<\/sub>\u2010Glycoprotein<\/scp> I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-9632","authenticated-orcid":false,"given":"Cecilia B.","family":"Chighizola","sequence":"first","affiliation":[{"name":"Pediatric Rheumatology Unit, ASST G. 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Pini\u2010CTO, University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danieli","family":"Andrade","sequence":"additional","affiliation":[{"name":"Reumatologia, University of Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-0975","authenticated-orcid":false,"given":"Maria","family":"Tektonidou","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic and Internal Medicine Laiko Hospital, National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Pengo","sequence":"additional","affiliation":[{"name":"Department of Cardiac Thoracic and Vascular Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-1043","authenticated-orcid":false,"given":"Guillermo","family":"Ruiz\u2010Irastorza","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n de Enfermedades Autoinmunes, Servicio de Medicina Interna Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea, BioCruces Health Research Institute, Hospital Universitario Cruces  Barakaldo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Michael","family":"Belmont","sequence":"additional","affiliation":[{"name":"Hospital for Joint Diseases, New York University  New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gerosa","sequence":"additional","affiliation":[{"name":"Clinical Rheumatology Unit, ASST G. Pini\u2010CTO, University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-2596","authenticated-orcid":false,"given":"Paul","family":"Fortin","sequence":"additional","affiliation":[{"name":"PMedicine, Universit\u00e9 Laval  Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Ware","family":"Branch","sequence":"additional","affiliation":[{"name":"Department of Obstetrics University of Utah and Intermountain Healthcare  Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9107-3218","authenticated-orcid":false,"given":"Laura","family":"Andreoli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1441-5373","authenticated-orcid":false,"given":"Michelle A.","family":"Petri","sequence":"additional","affiliation":[{"name":"Rheumatology, Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricard","family":"Cervera","sequence":"additional","affiliation":[{"name":"Department of Autoimmune Diseases Hospital Cl\u00ednic de Barcelona  Barcelona 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