The role of receptor molecules for IgA in the pathogenic mechanism of IgA nephropathy

本研究的目的是通过研究IgA分子受体及其代谢的动态，阐明IgA肾病中系膜IgA沉积的机制。三种分子，pIgR（聚合免疫球蛋白受体），FcαR和ASGPR（无糖糖蛋白受体），已被称为IgA的受体分子。此外，第四个分子，TfR（转铁蛋白受体），最近被确定为IgA的受体。研究表明，在IgAN患者肾小球中，TfR表达上调，提示TfR在该病中参与病理性免疫复合物的形成。在这项研究中，我们研究了这些受体分子的遗传多态性与IgAN的可能关联。然而，我们没有发现FcαR、ASGPR和TfR多态性与IgAN有任何显著关联。在过去的十年中，已经报道了几条证据线，表明IgAl铰链区域o -糖基化的不完全性可能是IgAl沉积的合理原因。o -聚糖存在于许多糖蛋白中，尤其是分泌性糖蛋白中。常见的核心o -聚糖结构Galb-1-3GalNAc-R是动物细胞表面许多延伸黏液型o -聚糖结构的前体，并分泌包括IgAl在内的糖蛋白。我们还在《肾脏国际》上发表了一篇关于这一概念的综述论文（Narita I, et al. 2007）。

The purpose of this study was to elucidate the mechanism of mesangial IgA deposition in IgA nephropathy, especially through investigating the dynamics of receptors for IgA molecules and their metabolisms. Three molecules, pIgR (polymeric immuno-globulin receptor), FcαR, and ASGPR (asyaloglycoprotein receptor), have been known as receptor molecules for IgA. In addition, fourth molecules, TfR (Transferrin receptor), has recently been identified as receptor of IgA. It has been shown that the expression of TfR is upregulated in glomeruli of patients with IgAN, suggesting that TfR plays a role in formation of pathological immune complex in this disease.In this study, we investigated the possible associations of genetic polymorphisms in these receptor molecules and IgAN. However, we did not find any significant association of FcαR, ASGPR, and TfR polymorphisms and IgAN.During the last decade, several lines of evidence have been reported indicating that incompleteness of O-glycosylation in the IgAl hinge region may be a plausible cause of the IgAl deposition. O-Glycans are found in many glycoproteins, particularly in secretory glycoproteins. The common core 1 O-glycan structure, Galb-1-3GalNAc-R, is a precursor for many extended mucin-type O-glycan structures on animal cell surfaces and secreted glycoproteins including IgAl. We also have published a review paper about this notion in Kidney International (Narita I, et al. 2007).