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The Complex Relatio...
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Grosso, GiorgiaKarolinska Institutet
(author)
The Complex Relationship between C4b-Binding Protein, Warfarin, and Antiphospholipid Antibodies
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-02-28
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Georg Thieme Verlag KG,2021
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Numbers
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LIBRIS-ID:oai:DiVA.org:lnu-101754
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https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-101754URI
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https://doi.org/10.1055/a-1347-5655DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-469032URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:146039041URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Background Low 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. Objectives To 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. Methods In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS, N =67), aPL++ individuals without clinical manifestations (aPL carriers, N =15), SLE-aPL++ ( N =118, among them, secondary [s] APS, N =56), aPL negative (-) SLE (SLE-aPL-, N =291), 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. Results Overall, 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%) Conclusion Both 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.
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Sandholm, KerstinLinnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Linnaeus Ctr Biomat Chem, BMC,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.(Swepub:lnu)jsake
(author)
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Antovic, AleksandraKarolinska Institutet
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Gunnarsson, IvaKarolinska Institutet
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Zickert, AgnetaKarolinska University Hospital, Sweden,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med Solna, Stockholm, Sweden.
(author)
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Vikerfors, AnnaSwedish Medical Products Agency, Sweden,Swedish Med Prod Agcy, Uppsala, Sweden.
(author)
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Truedsson, LennartLund University Hospital, Sweden,Lund Univ Hosp, Dept Microbiol Immunol & Glycobiol, Lund, Sweden.
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Bruzelius, MariaKarolinska Institutet
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Nilsson, BoUppsala universitet,Klinisk immunologi(Swepub:uu)bonils
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Nilsson Ekdahl, KristinaUppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden(Swepub:uu)krisnil
(author)
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Svenungsson, ElisabetKarolinska Institutet
(author)
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Karolinska InstitutetInstitutionen för kemi och biomedicin (KOB)
(creator_code:org_t)
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In:Thrombosis and Haemostasis: Georg Thieme Verlag KG121:10, s. 1299-13090340-62452567-689X
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Sandholm, Kersti ...
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Gunnarsson, Iva
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Zickert, Agneta
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Vikerfors, Anna
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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