Study of pathogenesis of IgA nephropathy

IgA肾病(IgAN)以IgA沉积为主的肾小球系膜病变和系膜增生性肾小球肾炎(GN)为特征。关于其发病机制，一些研究人员认为，沉积的IgA是一种针对病毒、细菌或饮食抗原的抗体。然而，在IgAN患者中分离特异性IgA循环免疫复合物相关抗原的尝试一直没有成功。我们已经证明，黏膜感染，如咽炎，通常与IgAN的急性发作有关。因此，IGAN是一种免疫复合体疾病，由患者长期接触的环境抗原的粘膜免疫反应不佳引起。我们已经观察到，副流感嗜血杆菌(HP)更多地从IgAN患者的咽部分离出来，而不是从其他疾病的患者中分离出来。我们还鉴定了Hp抗原的肾小球外膜沉积(Omhp)和…。IgAN患者血清中抗OMHP的IgA-Ab浓度升高越多。此外，我们还发现，IgAN患者通过针对OMHP的多克隆激活，特异性地增加了抗OMHP的IgA-Ab的产生，并将产物从一种同型转换为另一种，例如从IgM转换为IgA。我们的目的是阐明OMHP与IgAN患者或对照组扁桃体中的淋巴细胞之间的免疫反应。IgAN患者对OMHP的刺激指数明显高于对照组。IgA N患者淋巴细胞培养上清液中抗OMHP的IgA抗体和IgA1水平也显著高于对照组。经OMHP刺激后，IgA-抗体与IgG-Ab、IgA-抗体与IgM-Ab、抗OMHP抗体的IgG与IgM-Ab呈正相关，提示OMHP对IgA-N患者扁桃体T、B淋巴细胞的刺激作用，提示OMHP的免疫应答可能参与了IgAN的发病机制。较少

IgA nephropathy (IgAN) is characterized by the presence of IgA deposits, predominantly in the glomerular mesangium, and by mesangial proliferative glomerulonephritis (GN). Concerning its pathogenesis, several investigators have suggested that the deposited IgA is an antibody (Ab) to viral, bacterial or dietary antigens. Nevertheless, attempts to isolate a specific IgA circulating immune complex-associated antigen in patients with IgAN have been unsuccessful.We have shown that mucosal infection such as pharyngitis are often associated with the acute onset of IgAN. IgAN is, then, an immune complex disease that is caused by a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgAN than from those with other diseases. We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and a … More n increased serum concentration of IgA-Ab against OMHP in patients with IgAN. Furthermore, We have shown that patients with IgAN have a specific increase in the production of IgA-Ab against OMHP via polyclonal activation against these, with switching of production from one isotype to another, e. g. from IgM to IgA.Our objective was to clarify the immune response between OMHP and lymphocytes in tonsils from patients with IgAN or controls. Patients with IgAN showed a significantly higher level of stimulation index to OMHP than controls. Lymphocytes from patients with IgA N also showed a significant higher level of IgA Ab and IgA1 against OMHP in culture supernatants than those from controls. Patients with IgA N showed positive correlations between IgA- and IgG-Ab, between IgA- and IgM-Ab, and between IgG and IgM-Ab against OMHP after OMHP stimulation.These results suggest that OMHP stimulate tonsillar T- and B-lymphocytes in patients with IgA N and that the immune response to OMHP may play a role in the pathogenesis of IgAN. Less