study of pathogenesis of IgA neuropathy

IgA神经病发病机制的研究

• 批准号: 12671033
• 负责人: SUZUKI Satoru
• 金额: $ 2.18万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671033/
• 关键词: IgA nepnropathy; tonsil Haemophilus parainfluenzae; mucosal immunity; lymphocyte function; mouse model; cytokine; cytokine

IgA nephropathy (IgAN) is characterized by the presence of IqA deposits, predominantly in the qlomerular mesangium. Concerning its pathogenesis, several investigators have suggested that the glomerular IgA deposits in IgA N are antibodies (Ab) to viral, bacterial or dietary antigens Thus the Ab are probably produced as part of the specific host immune response to various environmental antigens. We have observed previously that Haemophilus parainfluenzae (HP) is more commonlyisolated from the pharynx of patients with IgAN than from those with other glomerular diseases. We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and an 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, and that a si … More gnificant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN, and that OMHP stimulate tonsillar B-lymphocvtes to produce specific lqA1-Ab against OMHP and tonsillar T-lvmphocytes in patients with IgAN.Our objective was to investigated the production of IgA and several cytokines by tonsillar lymphocytes (TL) from patients with IgAN induced by stimulation with OMHP. We used TL from the palatine tonsils of patients with IgAN and patients with chronic tonsillitis but without renal diseases as controls. HP was detected in the tonsils of all patients before tonsillectomy. We examined production of IgA-Ab against OMHP and cytokines in the culture supernatants after lymphocyte incubation with OMHP. The spontaneous production of total IgA and TGF-β by TL from patients with IgAN was higher than that by TL from controls. Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TL from patients with IgAN, but not by TL from controls. OMHP stimulation also enhanced the production of TGF-β and IL-10 by TL from patients with IgAN. Spontaneous IFN-γ production and spontaneous total IgA production by TL were higher in IgAN patients than in controls. IFN-γ induction by OMHP stimulation was also higher in IgAN patients than in controls. IFN-γ production was positively correlated with total IgA values in both IgAN patients and controls. Less

伊加肾病（IgAN）的特征是存在主要在肾小球系膜中的IqA沉积。关于其发病机制，一些研究者认为伊加N中的肾小球伊加沉积物是针对病毒、细菌或饮食抗原的抗体（Ab）。因此，Ab可能是作为对各种环境抗原的特异性宿主免疫应答的一部分而产生的。我们以前曾观察到副流感嗜血杆菌（HP）更常见于IgAN患者的咽部，而不是其他肾小球疾病患者。我们还确定了肾小球沉积外膜的HP抗原（OMHP）和血清中的IgA抗体浓度增加对OMHP的IgAN患者。此外，我们已经表明，IgAN患者通过多克隆激活抗OMHP的IgA-Ab的产生特异性增加，产生从一种同种型转换为另一种同种型，例如从IgM转换为伊加，并且这种特异性增加是由于IgA-Ab的产生是通过免疫球蛋白A（IgM）和IgA（IgA）来实现的。 ...更多信息 抗OMHP的IgA抗体与伊加肾病患者的肾脏损害有密切关系，OMHP可刺激IgA肾病患者扁桃体B淋巴细胞产生抗OMHP的特异性lqA 1抗体和扁桃体T淋巴细胞产生特异性lqA 1抗体。我们使用TL从腭扁桃体的IgAN患者和慢性扁桃体炎，但没有肾脏疾病的患者作为对照。所有患者扁桃体切除术前均检出HP。我们检测了淋巴细胞与OMHP孵育后培养上清中抗OMHP的IgA抗体和细胞因子的产生。IgAN患者TL自发产生的总伊加和TGF-β均高于对照组。OMHP体外刺激增强了IgAN患者TL的HP特异性伊加的产生，但对照组TL没有。OMHP刺激也可促进IgAN患者TL产生TGF-β和IL-10。IgAN患者的自发IFN-γ产生和TL自发总伊加产生均高于对照组。IFN-γ诱导OMHP刺激也高于IgAN患者比对照组。在IgAN患者和对照组中，IFN-γ的产生与总伊加值呈正相关。少

项目成果

Satoru Suzuki: "Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy"Clin Exp Immunol. 119. 328-332 (2000)

铃木悟：“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”Clin Exp Immunol。

Suzuki Satoru et al.: "Production of IgA, JGF-β and IL-10 by tonsillar mononuclear lymphocytes from Patients with IgA nephropathy induced by stimulation with Haemophilus parainfluenzae antigens"Nephrology. 6. A6 (2001)

Suzuki Satoru 等人：“副流感嗜血杆菌抗原刺激诱导的 IgA 肾病患者的扁桃体单核淋巴细胞产生 IgA、JGF-β 和 IL-10”，肾病学 6. A6 (2001)。

Chie Yamamoto: "Experimental nephropathy induced by Haemophilus parainfluenzae antigens"Nephron. (in press).

Chie Yamamoto：“副流感嗜血杆菌抗原诱导的实验性肾病”肾单位。

Fujieda Shigeharu et al.: "Production of interfered-γ by tonsillar mononuclear cells in IgA nephropathy patients"Acta Otolaryngol. 120. 649-654 (2000)

Fujieda Shigeharu 等：“IgA 肾病患者中扁桃体单核细胞产生干扰的 γ”Acta Otolaryngol. 120. 649-654 (2000)

Satoru Suzuki: "Synthesis of immunoglobulins against Haemophilus parainfluenzae by tonsillar lymphocytes from patients with IgA nephropathy"Nephrol Dial Transplant. 15. 619-624 (2000)

铃木悟：“IgA肾病患者的扁桃体淋巴细胞合成抗副流感嗜血杆菌的免疫球蛋白”肾拨号移植。