{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:01Z","timestamp":1790676601712,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"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 & Rheumatology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"Objective<\/jats:title>This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti\u2013neutrophil extracellular trap (anti\u2010NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody\u2013positive patients who did not have lupus.<\/jats:p><\/jats:sec>Methods<\/jats:title>Anti\u2010NET IgG\/IgM levels were measured in serum samples from 389 aPL\u2010positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n\u00a0=\u00a0214), we profiled autoantibodies using an autoantigen microarray platform.<\/jats:p><\/jats:sec>Results<\/jats:title>We found elevated levels of anti\u2010NET IgG and\/or IgM in 45% of the aPL\u2010positive patients. High anti\u2010NET antibody levels are associated with more circulating myeloperoxidase (MPO)\u2013DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti\u2010NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti\u2010NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti\u2010NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti\u2010NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO\u2013DNA complexes, and nucleosomes. Anti\u2010NET IgM positivity was associated with autoantibodies targeting single\u2010stranded DNA, double\u2010stranded DNA, and proliferating cell nuclear antigen.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These data reveal high levels of anti\u2010NET antibodies in 45% of aPL\u2010positive patients, where they potentially activate the complement cascade. While anti\u2010NET IgM may especially recognize DNA in NETs, anti\u2010NET IgG species appear to be more likely to target NET\u2010associated protein antigens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42489","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T10:54:12Z","timestamp":1677754452000},"page":"1407-1414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Anti\u2013Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody\u2013Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal<\/scp> Networking Clinical Database and Repository"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-7755","authenticated-orcid":false,"given":"Yu","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherwin","family":"Navaz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Tsodikov","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-4587","authenticated-orcid":false,"given":"Katarina","family":"Kmetova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, and Institute of Molecular Biomedicine, Faculty of Medicine Comenius University Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay","family":"Kluge","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amala","family":"Ambati","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire K.","family":"Hoy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi","family":"Yalavarthi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology University of Michigan Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danieli","family":"de Andrade","sequence":"additional","affiliation":[{"name":"University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-0975","authenticated-orcid":false,"given":"Maria G.","family":"Tektonidou","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-9441","authenticated-orcid":false,"given":"Savino","family":"Sciascia","sequence":"additional","affiliation":[{"name":"University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Pengo","sequence":"additional","affiliation":[{"name":"Padova University Hospital Padova 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":"Hospital Universitario Cruces, University of the Basque Country Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-2976","authenticated-orcid":false,"given":"H. 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