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Glycosyltransferase expression in IgA[superscript +] B cells in IgA nephropathy

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posted on 2014-05-16, 15:14 authored by Joanna Kathryn Fiona Boyd
IgA nephropathy is a common kidney disease classically presenting in the second to third decade with episodic haematuria following mucosal infection. Up to a third of patients will develop progressive renal failure requiring renal replacement therapy. IgA nephropathy is diagnosed on renal biopsy by finding deposits containing the immunoglobulin IgA in the renal mesangium. Deposited IgA has particular characteristics: it is typically polymeric, of the IgA1 subtype and the IgA1 hinge region tends to be poorly galactosylated when compared to circulating IgA1 from healthy subjects. IgA is synthesised by IgA-committed B cells usually in response to mucosal antigen encounter. Differential glycosylation of the IgA1 hinge region appears to be important in the normal human immune response and is controlled by specific glycosyl- and sialyl-transferases. Abnormalities in glycosyl- or sialyltransferase expression are therefore predicted to play a role in the generation of poorly galactosylated IgA1 which deposits in the renal mesangium of patients with IgA nephropathy. My aim was to define glycosyltransferase expression in circulating IgA-secreting B cells from patients and compare expression patterns with healthy subjects. We isolated IgA[superscript +] plasmablasts and memory B cells from peripheral blood samples by flow cytometry and interrogated them by quantitative PCR for mRNA expression of the glycosyltransferase C1GalT1 and its molecular chaperone Cosmc, both known to be important in IgA1 hinge region galactosylation. We found that IgA+ plasmablasts but not IgA[superscript +] memory B cells from patients tended to express higher levels of both C1GalT1 and Cosmc when compared to healthy subjects. This confirms previous suggestions that an enzyme abnormality is not global and we show that it may be localised to the IgA[superscript +] plasmablast population. Decreased IgA1 hinge region galactosylation would be predicted to be associated with lower levels of C1GalT1 expression and we speculate that our results demonstrate a compensatory response to poor galactosylation.

History

Supervisor(s)

Barratt, Jonathan; Molyneux, Karen

Date of award

2014-04-01

Author affiliation

Department of Infection, Immunity and Inflammation

Awarding institution

University of Leicester

Qualification level

  • Masters

Qualification name

  • Mphil

Language

en

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