1. ¹John Walls Renal Unit, Leicester General Hospital, Leicester, UK
2. ²Renal Unit, Queen Margaret Hospital, Dunfermline, UK
3. ³Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK

Correspondence: AC Smith, John Walls Renal Unit, Leicester General Hospital, Leicester LE4 5PW, UK. E-mail: aa50@le.ac.uk

⁴These authors contributed equally to this work

Received 20 August 2007; Revised 10 October 2007; Accepted 16 October 2007; Published online 5 March 2008.

Abstract

In IgA nephropathy (IgAN), pathogenic IgA1 is likely derived from bone marrow (BM) cells and exhibits reduced O-galactosylation. Defective O-galactosylation may arise from the compromised expression or function of the enzyme -galactosyltransferase and/or its molecular chaperone (Cosmc). We measured B-cell O-galactosylation activity and the relative gene expression of -galactosyltransferase and Cosmc in peripheral blood and BM taken from patients with IgAN and controls. O-galactosylation activity was measured in peripheral and BM B cells by the incorporation of radiolabeled galactose into an asialo-mucin acceptor. Gene expression of -galactosyltransferase and Cosmc was measured by real-time PCR and related to that of the enzyme GalNAc-T2 (UDP-N-acetyl--D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-2), which synthesizes the core O-glycan. Neither the B-cell O-galactosylation activity nor the gene expression of the enzyme or chaperone was different between patients and controls. However, the relationships between the O-glycosylation of serum IgA1, galactosylation activity, and -galactosyltransferase gene expression showed different patterns in IgAN and controls. In IgAN, O-galactosylation activity correlated with -galactosyltransferase gene expression, but not with IgA1 O-glycosylation, suggesting that factors other than the availability of -galactosyltransferase or Cosmc are responsible for altered IgA1 O-glycosylation.