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Title: An investigation into the biochemistry of β2glycoprotein I and the interaction of the fibrinolytic system with antiphospholipid antibodies
Author: Nash, Michael James
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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The antiphospholipid syndrome (APS), is an autoimmune condition characterised by the occurrence of thrombosis (both arterial and venous) and obstetric morbidity along with the persistent production of antiphospholipid antibodies (aPL). At present the pathophysiology of APS is unclear although several hypothesis are available in the literature. This thesis has aimed to examine some of the processes behind the APS focusing on the interaction of aPL with components of the fibrinolytic system and the interaction of Beta2 glycoprotein I (β2GPI) with fibrinolytic and other proteolytic enzymes. A detailed examination of our patient cohort was undertaken and compared to new serological criteria for APS. The interaction of aPL on plasmin mediated cleavage of β2GPI was examined and found to be reduced in the presence of some aPL. Plasma kallikrein and Xa were tested for proteolytic activity on β2GPI and found to posses this although to a lesser degree to that seen for plasmin. The effect of domain V genetic polymorphisms of βGPI on the action of plasmin on this part of the molecule was examined and found to be reduced in the presence of these polymorphisms. An investigation into the effect of one of these polymorphisms (Cys306Gly) on aPL production was undertaken with negative results in this respect. An examination of the effect of aPL on the binding of plasminogen to endothelial cell surfaces was undertaken and in some patient samples found to have an effect on this process. Moreover, some aPL were found to reduce fibrinolysis in a plasma clot lysis assay.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available