B-cell O-galactosyltransferase activity, and expression of O-glycosylation genes in bone marrow in IgA nephropathy.
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 beta-galactosyltransferase and/or its molecular chaperone (Cosmc). We measured B-cell O-galactosylation activity and the relative gene expression of beta-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 beta-galactosyltransferase and Cosmc was measured by real-time PCR and related to that of the enzyme GalNAc-T2 (UDP-N-acetyl-alpha-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 beta-galactosyltransferase gene expression showed different patterns in IgAN and controls. In IgAN, O-galactosylation activity correlated with beta-galactosyltransferase gene expression, but not with IgA1 O-glycosylation, suggesting that factors other than the availability of beta-galactosyltransferase or Cosmc are responsible for altered IgA1 O-glycosylation.
Buck
K S
KS
Renal Unit, Queen Margaret Hospital, Dunfermline, UK.
Smith
A C
AC
Molyneux
K
K
El-Barbary
H
H
Feehally
J
J
Barratt
J
J
D001402:B-Lymphocytes / Q000201:enzymology*; D001853:Bone Marrow; D005700:Galactosyltransferases / Q000235:genetics* / Q000502:physiology*; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000201:enzymology* / Q000235:genetics*; D006031:Glycosylation; D018832:Molecular Chaperones / Q000235:genetics* / Q000502:physiology*
C505369:C1GALT1C1 protein, human; D018832:Molecular Chaperones; D005700:Galactosyltransferases