{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:22:48Z","timestamp":1767187368196,"version":"3.48.0"},"reference-count":16,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"unspecified","delay-in-days":90,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L246007"],"award-info":[{"award-number":["L246007"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62071011"],"award-info":[{"award-number":["62071011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,12,14]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The diagnosis of antiphospholipid syndrome (APS) uses standard antibodies (lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG\/IgM, \u03b22-glycoprotein I antibodies (\u03b22GPI) IgG\/IgM), which results in some patients with \u2018seronegative APS\u2019 being overlooked. The diagnostic value of an extended antibody profile, including antiphosphatidylserine\/prothrombin complex (aPS\/PT) and aCL\/\u03b22GPI IgA, requires clarification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to define antibody heterogeneity in APS and determine the diagnostic and risk-stratification value of novel antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively enrolled 2994 patients with clinical features suggestive of APS who underwent testing for criteria antibodies (LAC, aCL IgG\/IgM and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI IgG\/IgM) and extended markers (aPS\/PT IgG\/IgM and aCL\/\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI IgA). Principal component analysis (PCA) explored antibody reactivity patterns. Multivariate logistic regression identified independent diagnostic predictors, and receiver operating characteristic curve analysis evaluated diagnostic performance. Associations between antibodies and clinical parameters defined clinical phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PCA revealed three dimensions explaining 73.56% of variance: principal component (PC)1 (IgG\/LAC axis; 41.42%), PC2 (specific IgM axis; 18.12%) and PC3 (specific IgA axis; 14.02%). aPS\/PT-IgM was a strong independent predictor of clinical diagnosis (adjusted OR 1.147, 95%\u2009CI 1.129 to 1.165, p&lt;0.001). The area under the curve for diagnosing triple-negative APS was 0.868 for aPS\/PT-IgM. Standard criteria antibodies lost independent significance in the full model. Phenotypic analysis identified three subtypes: a \u2018classical type\u2019 (PC1-High) with prolonged coagulation times and complement consumption; an \u2018inflammatory type\u2019 (PC3-High) with elevated systemic inflammation markers without complement consumption; and a \u2018restricted type\u2019 (PC2-High) associated with anaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Distinct antiphospholipid antibody heterogeneity exists, categorisable into \u2018classical\u2019, \u2018inflammatory\u2019 and \u2018restricted\u2019 subtypes. This study identifies aPS\/PT-IgM as a strong independent serological marker associated with clinical status. Incorporating aPS\/PT-IgM into routine testing could significantly reduce seronegative APS misdiagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006406","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:55:20Z","timestamp":1767182120000},"page":"e006406","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Heterogeneity of antiphospholipid antibody profiles in a clinical cohort and association with distinct clinical features"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7514-930X","authenticated-orcid":false,"given":"Zhongjun","family":"Shen","sequence":"first","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center, Beijing, China"},{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangjia","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuying","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huike","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center, Beijing, China"},{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center, Beijing, China"},{"name":"Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"2025123105200795000_11.4.e006406.1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/bjh.14632","article-title":"Pathogenesis and management of antiphospholipid syndrome","volume":"178","author":"Arachchillage","year":"2017","journal-title":"Br J Haematol"},{"key":"2025123105200795000_11.4.e006406.2","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1002\/art.42624","article-title":"The 2023 ACR\/EULAR Antiphospholipid Syndrome Classification Criteria","volume":"75","author":"Barbhaiya","year":"2023","journal-title":"Arthritis Rheumatol"},{"key":"2025123105200795000_11.4.e006406.3","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtauto.2021.100134","article-title":"Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome","volume":"4","author":"Devreese","year":"2021","journal-title":"J Transl 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APS","volume":"63","author":"Li","year":"2024","journal-title":"Rheumatology (Oxford)"},{"key":"2025123105200795000_11.4.e006406.10","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1055\/s-0040-1714653","article-title":"Is There an Additional Value in Detecting Anticardiolipin and Anti-\u03b22 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?","volume":"120","author":"Chayoua","year":"2020","journal-title":"Thromb Haemost"},{"key":"2025123105200795000_11.4.e006406.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.04.011"},{"key":"2025123105200795000_11.4.e006406.12","doi-asserted-by":"publisher","DOI":"10.1177\/1076029612437578"},{"key":"2025123105200795000_11.4.e006406.13","first-page":"638","article-title":"Laboratory Evaluation of Antiphospholipid Syndrome","volume":"152","author":"Heikal","year":"2019","journal-title":"Am J Clin 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