Use this URL to cite or link to this record in EThOS:
Title: The role of the bone marrow in immunoglobulin A nephropathy
Author: Buck, Katharine
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2006
Availability of Full Text:
Access from EThOS:
Access from Institution:
Lectin-binding and electrophoresis studies have indicated that the abnormality of IgAl O-glycosylation in IgAN takes the form of reduced terminal galactosylation. O-galactosylation is effected by the intracellular enzyme beta1,3galactosyltransferase (beta1,3GT) during synthesis of IgAl by cells of the B lineage, and compromised activity of this enzyme may underlie altered O-glycosylation in IgAN. This study tested the hypothesis that undergalactosylation of IgA1 is due to reduced B cell beta1,3GT activity, focussing on the bone marrow, the putative source of mesangial IgAl in IgAN.;An assay for cellular beta1,3GT activity, measuring the incorporation of (14C)galactose into asialo-ovine submaxillary mucin (aOSM), was established and optimised. Peripheral blood (PB) and BM cell types were purified on antibody-conjugated magnetic beads, and their enzyme activity measured in comparison to a standard cell line.;An initial set of experiments was performed using peripheral blood (PB) B and T cells from ten IgAN patients and ten controls with no difference in beta1,3GT activity being found. However, technical problems were encountered, which were addressed and improvements made. Subsequently, beta1,3GT activity of BM B cells and reticulocytes, and PB B cells from 12 IgAN patients and 13 controls was measured. No abnormality of beta1,3GT activity was seen in IgAN, despite demonstrating reduced terminal galactosylation of serum IgAl in the patient group.;These results do not implicate abnormal function of beta1,3GT as the cause of abnormal IgAl O-glycosylation in IgAN. Altered beta1,3GT activity in a minor subset of cells, or abnormalities of other glycosyltranferases, remain a possibility and should be investigated further.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available