Humoral immunity against the proline-rich peptide epitope of the IgA1 hinge region in IgA nephropathy

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 ). Introduction We describe here the presence of humoral immunity against the IgA1 hinge peptide epitope in IgAN and IgA nephropathy (IgAN ) is the most common glomerevaluate the relationship between the underglycosyl- ular disease which is characterized immunohistologation of the IgA1 hinge region and humoral immunity. ically by the predominant deposition of the IgA1 Method. The serum anti-IgA1 hinge peptide antibody subclass in the mesangial area [1,2]. The structural (anti-a1HP ab) titre was measured and compared characteristics of the IgA1 molecule recently were between the IgAN (n=37) and control groups (n=34) associated with the pathogenesis of IgAN, because the by enzyme-linked immunosorbent assay ( ELISA) IgA1 molecule is obviously diVerent from the other using a synthetic peptide corresponding to the human immunoglobulins in its hinge region which is a unique IgA1 hinge region, PVPSTPPTPSPSTPPTPSPS, as an mucin-like glycopeptide. The IgA1 hinge region has a antigen. Next, to evaluate the relationship between the proline-, serine- and threonine-rich amino acid underglycosylation of the IgA1 hinge region and the sequence in which the serine and threonine residues humoral immunity, the reactivity of the serum IgG are able to carry O-linked oligosaccharides consisting from the patients with IgAN against monoclonal IgA1 of sialic acid (NeuNAc), galactose (Gal ) and Nwhich had been digested enzymatically to remove the acetylgalactosamine (GalNAc) with microheterocarbohydrates from the IgA1 hinge region was meas- geneity [3,4]. Some investigators, including us, revealed ured by ELISA. the presence of defective O-glycans in the hinge region Results. The anti-a1HP ab titre was significantly higher of the IgA1 molecules derived from sera of patients in the IgAN group than in the control group (OD with IgAN [5‐9]. Additionally, we showed that the value: IgG class, 0.564±0.344 vs 0.331±0.154, P= core peptide of the IgA1 hinge region was exposed by 0.0014; IgM class, 0.272±0.148 vs 0.141±0.072, its underglycosylation in IgAN using a rabbit polyP