Lupus antibody bivalency is required to enhance prothrombin binding to phospholipid

The Journal of Immunology : Official Journal of the American Association of Immunologists
S L FieldP J Hogg

Abstract

Lupus anticoagulants (LA) are a family of autoantibodies that are associated with in vitro anticoagulant activity but a strong predisposition to in vivo thrombosis. They are directed against plasma phospholipid-binding proteins including prothrombin. We have proposed that LA propagates coagulation in flowing blood by facilitating prothrombin interaction with the damaged blood vessel wall. A murine monoclonal anti-prothrombin Ab and three of three LA IgGs enhanced prothrombin binding to 75:25 phosphatidyl choline:phosphatidyl serine vesicles measured by either ultracentrifugation or right-angle light scattering. The assembly of prothrombin and LA IgG on phospholipid vesicles was estimated by surface plasmon resonance. The on rates for prothrombin and LA IgG were approximately the same as the on rate for prothrombin alone. In contrast, the off rates for prothrombin and LA IgG were 2- to 3-fold slower than the off rate for prothrombin. LA IgG bivalency was required for enhanced prothrombin binding to phospholipid vesicles, as Fab of the LA IgGs did not influence prothrombin binding at concentrations up to 40 microM. Modeling of the interactions of prothrombin, LA IgG and phospholipid vesicles indicated that augmentation of prothro...Continue Reading

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Citations

Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Nov 5, 2002·Annual Review of Medicine·Jacob H Rand
Feb 5, 2005·Pathophysiology of Haemostasis and Thrombosis·Monica Galli
Apr 29, 2006·British Journal of Haematology·Angela M PattersonMike Greaves
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paolo D'AgnilloJoyce Rauch
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·J Arnout, J Vermylen
Jan 10, 2021·Journal of Thrombosis and Haemostasis : JTH·Tessa NoordermeerRolf T Urbanus
Jul 9, 2004·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Edouard M BeversGeorge M Willems
Jul 10, 2003·Clinics in Laboratory Medicine·Neal S Rote, Bradley P Stetzer

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