التفاصيل البيبلوغرافية
| العنوان: |
Anti-β2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies interfere with cleavage of factor V(a) by activated protein C |
| المؤلفون: |
Noordermeer, Tessa, Chemlal, Soumaya, Jansma, Janna J, van der Vegte, Vossa, Schutgens, Roger E G, Limper, Maarten, de Groot, Philip G, Meijers, Joost C M, Urbanus, Rolf T |
| المساهمون: |
Poli Van Creveldkliniek Medisch, Child Health, Circulatory Health, Infection & Immunity, MS Reumatologie/Immunologie/Infectie |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
activated protein C resistance, antiphospholipid antibodies, lupus anticoagulant, prothrombin, β2-glycoprotein I, Hematology, Journal Article |
| الوصف: |
BACKGROUND: The acquired thrombotic risk factor known as lupus anticoagulant (LA) interferes with laboratory clotting assays and can be caused by autoantibodies against β2-glycoprotein I (β2GPI) and prothrombin. LA is associated with activated protein C (APC) resistance, which might contribute to thrombotic risk in patients with antiphospholipid syndrome. How antibodies against β2GPI and prothrombin cause APC resistance is currently unclear. OBJECTIVES: To investigate how anti-β2GPI and antiphosphatidylserine/prothrombin (PS/PT) antibodies induce APC resistance. METHODS: The effects of anti-β2GPI and anti-PS/PT antibodies on APC resistance were studied in plasma (of patients with antiphospholipid syndrome) and with purified coagulation factors and antibodies. RESULTS: APC resistance was observed in LA-positive patients with anti-β2GPI or anti-PS/PT antibodies and in normal plasma spiked with monoclonal anti-β2GPI or anti-PS/PT antibodies with LA activity. Analysis of factor (F)V cleavage patterns after APC incubation indicated that anti-β2GPI antibodies attenuated APC-mediated FV cleavage at R506 and R306. APC-mediated cleavage at R506 is required for FV cofactor activity during inactivation of FVIIIa. Assays with purified coagulation factors confirmed that anti-β2GPI antibodies interfered with the cofactor function of FV during FVIIIa inactivation but not with FVa inactivation. Anti-PS/PT antibodies attenuated APC-mediated FVa and FVIIIa inactivation. Analysis of FV(a) cleavage patterns after APC incubation indicated that anti-PS/PT antibodies interfere with APC-mediated cleavage of FV at positions R506 and R306. CONCLUSION: Anti-β2GPI antibodies with LA activity contribute to a procoagulant state by causing APC resistance via interference with the cofactor function of FV during FVIIIa inactivation. LA-causing anti-PS/PT antibodies interfere with the anticoagulant function of APC by preventing FV(a) cleavage. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1538-7933 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/449492Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/449492Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.8904F791 |
| قاعدة البيانات: |
BASE |
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