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IgA glycosylation in IgA nephropathy.

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thesis
posted on 19.11.2015, 09:05 by Alice. Allen
IgA nephropathy (IgAN) is a common glomerulonephritis characterised by deposition of IgA1 in the glomerular mesangium The underlying abnormality lies within the IgA system rather than the kidney, and modest irregularities of IgA biology have been described, but the mechanisms involved in IgA1 deposition and glomerular injury remain elusive. A few reports have suggested an abnormality of the carbohydrate component of IgA1 in IgAN. These studies sought to confirm and further characterise the putative glycosylation defect and to identify its biochemical basis. Lectin binding assays were developed and used to analyse the N- and O-linked glycans of IgA1 in IgAN and controls. No gross abnormality of N-glycosylation was detected in IgAN, though these studies were subject to technical limitations. IgA1 in IgAN displayed significantly increased binding to lectins with affinity for O-linked N-acetylgalactosamine (Ga1NAc) as compared to controls. One explanation for this finding is reduced terminal galactosylation of the O-linked sugars of IgA1. A novel assay was developed to measure the functional activity of alpha1,3 galactosyltransferase (alpha1,3GT), the enzyme responsible for O-galactosylation, in cell lysates. In IgAN, peripheral blood B cells appeared to show significantly lower alpha1,3GT activity than controls, and this was inversely proportional to Ga1NAc expression of serum IgA1 as measured by lectin binding. These studies confirm an abnormality of O-linked glycosylation of serum IgA1 in IgAN, which may be attributed to low B cell alpha1,3GT activity. Altered O-glycosylation of IgA1 may be relevant to the pathogenesis of IgAN.

History

Date of award

01/01/1995

Author affiliation

Geology

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

PhD

Language

en

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