Nephrol Dial Transplant (2000) 15: 28-33
© 2000 European Renal Association-European Dialysis and Transplant Association
Humoral immunity against the proline-rich peptide epitope of the IgA1 hinge region in IgA nephropathy
Department of Medicine and 1 Department of Biochemistry, School of Medicine, Kitasato University, Sagamihara-City and 2 Analytical Research Center, Asahi Chemical Industry Co., Ltd, Fuji-City, Japan
Correspondence and offprint requests to: Tohru Kokubo MD, Department of Medicine, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Background. The human IgA1 hinge region is a unique mucin-like O-linked proline-rich glycopeptide, and its core peptide was found to be exposed aberrantly by the underglycosylation in IgA nephropathy (IgAN). We describe here the presence of humoral immunity against the IgA1 hinge peptide epitope in IgAN and evaluate the relationship between the underglycosylation of the IgA1 hinge region and humoral immunity.
Method. The serum anti-IgA1 hinge peptide antibody (anti-
1HP ab) titre was measured and compared between the IgAN (n=37) and control groups (n=34) by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the human IgA1 hinge region, PVPSTPPTPSPSTPPTPSPS, as an antigen. Next, to evaluate the relationship between the underglycosylation of the IgA1 hinge region and the humoral immunity, the reactivity of the serum IgG from the patients with IgAN against monoclonal IgA1 which had been digested enzymatically to remove the carbohydrates from the IgA1 hinge region was measured by ELISA.
Results. The anti-1HP ab titre was significantly higher in the IgAN group than in the control group (OD value: IgG class, 0.564±0.344 vs 0.331±0.154, P=0.0014; IgM class, 0.272±0.148 vs 0.141±0.072, P<0.0001) and it was positive in ~40% of the patients with IgAN. In addition, the reactivity of the serum IgG from the IgAN patients against the monoclonal IgA1 was found to be increased as the carbohydrates were enzymatically removed from the IgA1 hinge region (when native=100; asialo, 122±9.5; agalacto, 167±11.5; naked, 188±3.9).
Conclusion. These results suggested that the peptide epitope of the IgA1 hinge region which was aberrantly exposed by underglycosylation could induce the humoral immune response in IgAN.
Keywords: IgA nephropathy; humoral immunity; IgA1 hinge region; proline-rich peptide; O-glycosylation
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