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Title: Investigation of contaminants with immunomodulatory activity in coagulation factor concentrates
Author: Pearson, Helen
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The results demonstrate that all conventional and ion-exchange chromatographically purified coagulation factor concentrates inhibit lymphocyte proliferation in vitro. These concentrates also contain measurable amounts of active TGF-β. In contrast, immunoaffinity purified and recombinant coagulation factor concentrates do not inhibit lymphocyte proliferation and contain very little active TGF-β. The levels of TGF-β detected in coagulation factor concentrates correlated with the degree of inhibition of lymphocyte proliferation. However, the amount of TGF-β present in the concentrates could account for only a small portion of the inhibitory activity. In addition, neutralising antibody specific to TGF-β only partially reversed the inhibitory effects that concentrates had on lymphocyte proliferation. In conclusion while TGF-β is present in concentrates, the amount detectable (and its relative potency) suggest it is only a minor immunosuppressive contaminant in coagulation factor concentrates. Part of the inhibitory activity of some higher purity products was removed by dialysis, suggesting that low molecular weight components, such as citrate were responsible for a proportion of the inhibitory activity of these products. Gel filtration experiments on an ion-exchange purified factor VIII concentrate suggest the presence of several inhibitory components which appear variably in different batches of this concentrate. Six peaks of lymphocyte proliferation inhibitory activity were detected, one with a molecular weight of >970 kDa, three peaks of inhibitory activity with molecular weights of approximately 550 kDa, 220 kDa, 120 kDa, a peak with a molecular weight <68 kDa and one with a molecular weight of approximately 6.5 kDa. The inhibitory fractions with molecular weight <68 kDa contained active TGF-β and the fractions with a molecular weight of approximately 6.5 kDa were confirmed to be low molecular weight components used in the formulation of this product. The four high molecular weight components were not identified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available