{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:27Z","timestamp":1790676627345,"version":"4.1.0"},"reference-count":50,"publisher":"Georg Thieme Verlag KG","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background\u2003Low levels of total C4b-binding protein (C4BPt), a circulating inhibitor of the classical\/lectin complement pathways, were observed in patients with antiphospholipid antibodies (aPLs) and during warfarin treatment.<\/jats:p><jats:p>Objectives\u2003To investigate the associations between aPL and C4BPt in patients with persistently positive (++) aPL, with\/without clinical manifestations and systemic lupus erythematosus (SLE), and in controls. Furthermore, we explored the impact of anticoagulation on C4BPt and in relation to complement activation.<\/jats:p><jats:p>Methods\u2003In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS, N\u2009=\u200967), aPL++ individuals without clinical manifestations (aPL carriers, N\u2009=\u200915), SLE-aPL++ (N\u2009=\u2009118, among them, secondary [s] APS, N\u2009=\u200956), aPL negative (\u2212) SLE (SLE-aPL\u2212, N\u2009=\u2009291), and 322 controls. Clinical characteristics, including treatment, were tabulated. C4BPt was determined with a magnetic bead method. Complement proteins (C1q, C2, C3, C4, C3a, C3dg, sC5b-9, factor I [FI]) were measured. A mediation analysis was performed to decompose the total effect of aPL++ on C4BPt into the direct and indirect effects of aPL++ through warfarin.<\/jats:p><jats:p>Results\u2003Overall, C4BPt is 20% decreased in aPL++ patients, regardless of SLE, APS, clinical manifestations, and aPL profile. C4BPt levels associate positively with complement proteins C1q, C2, C3, and C4, and negatively with complement activation product C3dg. In the SLE group, warfarin treatment contributes to approximately half of the C4BPt reduction (9%)<\/jats:p><jats:p>Conclusion\u2003Both aPLs and warfarin are associated with C4BPt reduction. Complement activation in aPL++ patients may partly be explained by impaired inhibition through depressed C4BPt levels. Further studies are needed to understand the clinical implications.<\/jats:p>","DOI":"10.1055\/a-1347-5655","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T23:57:19Z","timestamp":1610063839000},"page":"1299-1309","source":"Crossref","is-referenced-by-count":9,"title":["The Complex Relationship between C4b-Binding Protein, Warfarin, and Antiphospholipid Antibodies"],"prefix":"10.1055","volume":"121","author":[{"given":"Giorgia","family":"Grosso","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Sandholm","sequence":"additional","affiliation":[{"name":"Linnaeus Center for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Antovic","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agneta","family":"Zickert","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vikerfors","sequence":"additional","affiliation":[{"name":"Swedish Medical Products Agency, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart","family":"Truedsson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Glycobiology, Lund University Hospital, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bruzelius","sequence":"additional","affiliation":[{"name":"Department of Haematology, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Nilsson-Ekdahl","sequence":"additional","affiliation":[{"name":"Linnaeus Center for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-3244","authenticated-orcid":false,"given":"Elisabet","family":"Svenungsson","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,2,28]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","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":"S Miyakis","year":"2006","journal-title":"J Thromb 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