{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:19:29Z","timestamp":1776755969948,"version":"3.51.2"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3\/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and\/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4\/31 (13%) patients had decreased C3\/C4, while 7\/29 (24%) had elevated BC4d, 11\/33 (33%) EC4d, and 12\/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3\/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS\/TP\/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3\/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3\/C4, and the poor inverse correlation between CB-CAPs and C3\/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1459842","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T21:38:22Z","timestamp":1726695502000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases"],"prefix":"10.3389","volume":"15","author":[{"given":"Doruk","family":"Erkan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joann","family":"Vega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"O\u2019Malley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Concoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705454","article-title":"Diagnosis and management of the antiphospholipid syndrome","volume":"378","author":"Garcia","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2017.04.001","article-title":"Validation of a multi-analyte panel with cell-bound complement activation products for systemic lupus erythematosus","volume":"446","author":"Dervieux","year":"2017","journal-title":"J Immunol Methods"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1361.083","article-title":"Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome","volume":"1051","author":"Pierangeli","year":"2005","journal-title":"Ann N Y Acad Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","article-title":"International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)","volume":"4","author":"Miyakis","year":"2006","journal-title":"J Thromb Haemostasis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/art.34669","article-title":"Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus","volume":"64","author":"Kalunian","year":"2012","journal-title":"Arthritis Rheumatism"},{"key":"B6","doi-asserted-by":"publisher","first-page":"109828","DOI":"10.1016\/j.clim.2023.109828","article-title":"Complement biomarkers in the antiphospholipid syndrome - Approaches to quantification and implications for clinical management","volume":"257","author":"Cole","year":"2023","journal-title":"Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.10.879","article-title":"Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies","volume":"196","author":"Shamonki","year":"2007","journal-title":"Am J Obstet Gynecol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.090670","article-title":"Complement activation in patients with primary antiphospholipid syndrome","volume":"68","author":"Oku","year":"2009","journal-title":"Ann Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00773","article-title":"Blood cell-bound C4d as a marker of complement activation in patients with the Antiphospholipid syndrome","volume":"10","author":"Lonati","year":"2019","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2019-000318","article-title":"Platelet-bound C4d, low C3 and lupus anticoagulant associate with thrombosis in SLE","volume":"6","author":"Petri","year":"2019","journal-title":"Lupus Sci Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/art.21627","article-title":"Platelet C4d is highly specific for systemic lupus erythematosus","volume":"54","author":"Navratil","year":"2006","journal-title":"Arthritis Rheumatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1459842\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T21:38:23Z","timestamp":1726695503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1459842\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,17]]},"references-count":11,"alternative-id":["10.3389\/fimmu.2024.1459842"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1459842","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,17]]},"article-number":"1459842"}}