Nephrology Dialysis Transplantation, Vol 12, Issue 4 701-706, Copyright © 1997 by Oxford University Press
AC Allen, PS Topham, SJ Harper and J Feehally
BACKGROUND: Reduced galactosylation of the O-linked glycans of the IgA1
hinge region in IgAN has recently been described. To investigate the
underlying defect resulting in this abnormality, we have measured the
activity of beta 1,3 galactosyltransferase, the enzyme responsible for
galactosylation of O-linked sugars. METHODS: A galactose-acceptor substrate
was prepared from degalactosylated hinge region fragments of normal IgA1,
and incubated with the T cell, B cell, and monocyte lysates from patients
with IgAN and controls for acceptor regalactosylation. The extent of
acceptor galactosylation was then measured with biotinylated Vicia villosa
lectin (VV), which is specific for ungalactosylated moieties. Lectin
binding of serum IgA from the same subjects was also measured. RESULTS: T
cell and monocyte beta 1,3 galactosyltransferase activities did not differ
between IgAN and control, but B cell lysates in IgAN showed significantly
lower beta 1,3 galactosyltransferase activity than control (6.2 +/- 0.71
vs. 9.5 +/- 1.03 AU/microgram, P = 0.018). Furthermore, B cell beta 1,3
galactosyltransferase activity showed a negative correlation (r = - 0.87, P
= 0.002) with VV lectin binding of serum IgA in IgAN, but not controls.
CONCLUSIONS: These data indicate that altered IgA1 O- galactosylation in
IgAN results from a B cell-restricted reduction of beta 1,3
galactosyltransferase activity. This enzyme defect may be a fundamental
pathogenic abnormality in IgAN.
ORIGINAL ARTICLES
Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy
Department of Nephrology, Leicester General Hospital, UK.
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