Nephrology Dialysis Transplantation, Vol 14, Issue 1 81-85, Copyright © 1999 by Oxford University Press
T Kokubo, Y Hiki, H Iwase, A Tanaka, J Nishikido, K Hotta and Y Kobayashi
Background: The human IgA1 hinge region is a very
unique O-linked glycopeptide, and its sialylation and
galactosylation recently were reported to be defective in the serum IgA1
derived from patients with IgA nephropathy (IgAN). This study was performed
to examine the underglycosylation of the IgA1 hinge region and consequent
exposure of the peptide core in IgAN. Methods: A
polyclonal antibody against a synthetic human IgA1 hinge peptide,
PVPSTPPTPSPSTPPTPSPS, (anti-sHP ab) was raised in rabbits and shown
specifically to recognize the IgA1 which was treated with neuraminidase,
{beta}-galactosidase and &agr;-N-acetylgalactosaminidase. The
reactivity of the anti-sHP ab against the purified serum IgA1 was compared
among the following three groups; 39 patients with IgAN, 30 patients with
other renal diseases (ORD) and 21 healthy controls (HC) using an
enzyme-linked immunosorbent assay. Results: The
reactivity was significantly higher in the IgAN group (mean±SD
of OD 490 nm; 0.327±0.059) than in the ORD group
(0.274±0.043, P=0.0002) and in the HC group
(0.265±0.037, P<0.0001). No significant difference was
observed between the latter two groups. The frequency of positive cases
(gt;mean±2SD of HC) was 46.2% (18/39) in the IgAN group, 6.7%
(2/30) in the ORD group and 0% (0/21) in the HC group.
Conclusions: It was suggested that the peptide core of
the IgA1 hinge region is exposed aberrantly by a defective
N-acetylgalactosaminylation and plays a possible role in the pathogenesis
of IgAN. Key words: IgA1 hinge region; IgA
nephropathy; proline-rich peptide; O-glycosylation
ORIGINAL ARTICLES
Exposed peptide core of IgA1 hinge region in IgA nephropathy
Department of Medicine and Department of Biochemistry, School of Medicine, Kitasato University and Analytical Research Center, Asahi Chemical Industry Co., Ltd, Fuki-city, Japan; Corresponding author at: Department of Medicine, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara-city, Kanagawa 228, Japan
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