Nephrology Dialysis Transplantation, Vol 13, Issue 8 1980-1983, Copyright © 1998 by Oxford University Press
M Greer, J Barratt, S Harper, A Allen and J Feehally
Background. Mesangial IgA1 deposition is
characteristic of IgA nephropathy (IgAN). Structural abnormalities of the
IgA1 glycoprotein may play a key role in its mesangial deposition,
particularly the recently described abnormalities of O-glycosylation of the
IgA1 hinge region. The mechanism of abnormal O-glycosylation has not yet
been elucidated; it is not clear whether there is an alteration in the
amino acid sequence of the hinge region, modifying the number of
O-glycosylation sites available, or whether there is a post-translational
defect in the glycosylation processes. Methods. The
O-glycosylation of serum IgA1 from a series of patients with IgAN and
matched controls was assessed by lectin binding assay. We then used
dideoxysequencing of the PCR-amplified hinge region of the agr;1 heavy
chain gene to compare the hinge region nucleotide sequence in IgAN and
controls. We also compared cDNA transcripts of &agr;1 hinge region mRNA
to look for evidence for a transcriptional abnormality in IgAN.
Results. Lectin binding assays confirmed that the IgAN
subjects used in this study did indeed display the previously reported
abnormality of IgA1 O-glycosylation. However, the hinge region nucleotide
sequence of the &agr;1 gene was identical in IgAN and controls. There
was also no difference in the sizes of cDNA transcripts of hinge region
mRNA from patients with IgAN and controls.
Conclusions. We found no evidence for any nucleotide
sequence alteration or transcriptional abnormality of the &agr;1 hinge
region in IgAN, and we conclude that the O-glycosylation defect is
post-translational.
ORIGINAL ARTICLES
The nucleotide sequence of the IgA1 hinge region in IgA nephropathy
Department of Nephrology, Leicester General Hospital, Leicester, UK; Richard Bright Renal Unit, Southmead Hospital, Bristol, UK; Correspondence to: J Feehally, Department of Nephrology, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK
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