Study of pathogenesis of IgA nephropathy

IgA肾病发病机制研究

• 批准号: 10670991
• 负责人: SUZUKI Satoru
• 金额: $ 1.92万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670991/
• 关键词: IgA nephropathy; tonsil; Haemophilus parainfluenzae; outer membrane; lymphocyte; lymphocyte function; cytokine

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

伊加肾病（IgAN）的特征在于伊加沉积物的存在，主要在肾小球系膜中，以及系膜增生性肾小球肾炎（GN）。关于其发病机制，一些研究者认为沉积的伊加是针对病毒、细菌或饮食抗原的抗体（Ab）。然而，试图分离出一种特异性伊加循环免疫复合物相关抗原的IgAN患者一直unsuccessful.We已经表明，粘膜感染，如咽炎往往与急性发作的IgAN。IgAN是一种免疫复合物疾病，由对患者长期暴露的环境抗原的不良粘膜免疫应答引起。我们以前已经观察到，副流感嗜血杆菌（HP）更常见于IgAN患者的咽部，而不是其他疾病。我们还鉴定了HP抗原外膜的肾小球沉积（OMHP）， ...更多信息 IgAN患者血清中抗OMHP的IgA-Ab浓度升高。此外，我们已经表明，IgAN患者通过针对OMHP的多克隆活化，具有针对OMHP的IgA-Ab的产生的特异性增加，其中产生从一种同种型转换为另一种，例如。G.我们的目的是阐明OMHP与IgAN患者或对照组扁桃体中淋巴细胞之间的免疫应答。IgAN患者对OMHP的刺激指数显著高于对照组。伊加N患者的淋巴细胞培养上清中伊加Ab和IgA 1水平也显著高于对照组。伊加N患者经OMHP刺激后，伊加-Ab与IgG-Ab、伊加-Ab与IgM-Ab、IgG与IgM-Ab呈正相关，提示OMHP刺激伊加N患者扁桃体T、B淋巴细胞，对OMHP的免疫应答可能在IgA N的发病中起作用。少

项目成果

Satoru Suzuki: "Synthesis of immunoglobulins against Haemophilus parainfluenzae by tonsillar iymphocytes from patients with igA nephropathy"Nephrology Dialysis Transplantation. (in press).

铃木悟：“igA肾病患者扁桃体淋巴细胞合成抗副流感嗜血杆菌的免疫球蛋白”肾病透析移植。

Chie Yamamoto: "Experimental IgA nephropathy induced by Haemophilus parainfluenzae antigens"Nephrology. 5. A4 (1999)

Chie Yamamoto：“副流感嗜血杆菌抗原诱导的实验性 IgA 肾病”肾脏病学。

山本智恵: "Haemophilus parainfluenzae(HP)菌体外膜抗原を用いたIgA腎症モデル作成の試み" IgA腎症研究会 抄録. 22巻. 4 (1999)

Chie Yamamoto：“尝试使用副流感嗜血杆菌 (HP) 外膜抗原创建 IgA 肾病模型”IgA 肾病研究组摘要 22. 4 (1999)。

山本智恵: "Haemophilus parainfluenzae(HP)菌体外膜抗原を用いたIgA腎症モデル作成の試み"IgA腎症研究会 抄録. 22巻. 4 (1999)

Chie Yamamoto：“尝试使用副流感嗜血杆菌 (HP) 外膜抗原创建 IgA 肾病模型”IgA 肾病研究组摘要 22. 4 (1999)。

Suzuki Satoru et al.: "Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy"Clinical and Experimental Immunology. (in press).

铃木悟等人：“IgA肾病患者扁桃体淋巴细胞对副流感嗜血杆菌的免疫反应”临床和实验免疫学。