IgA specific helper cytokines in IgA nephropathy

IgA 肾病中的 IgA 特异性辅助细胞因子

• 批准号: 02670289
• 负责人: SAKAI Hideto
• 金额: $ 1.6万
• 依托单位: TOKAI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670289/
• 关键词: IgA nephropathy; Hyperproduction of IgA; Switch T cell; IL-4; IL-5; TGF-beta; IL-6; IgA産生能; サイトカイン; ILー4; ILー5; ILー6; TGFーβ; T_<α4>細胞

It is well known that IgA nephropathy is mediated by IgA-dominant immune complexes although the pathogenesis for inducing such immune complexes is unknown.The aim of the present study was to elucidate cytokines which are responsible for increased production of IgA observed in patients with IgA nephropathy and in some of their relatives. Fifty six patients with IgA nephropathy and 96 family members were studies. Fifty four healthy adults were served as controls. Peripheral blood mononuclear cells (PBMC) were separated and B-cell rich fraction as well as Talpha4 cells (i.e.IgA specific helper T cells) were concentrted by immune absorption technique. Interleukin 4, 5 aad 6 (IL-4, IL-5, IL-6) and tissue growth factor (TGF-beta) were cocultured with these B and T cell cultures alone or in combined forms. IgG, IgA, and IgM-bearing cells in these cultures were quantitated by flow cytometry. Concentration of IgG, IgA, IgM and IgE were measured by ELISA.There was no significant increase of IgA production in cultures with IL-5, IL-6 and TGF-beta. However, IL-4 induced significant increase in IgA-bearing cells and supernatant IgA in cultures with this cytokine with and without addition of IL-6.IL-6 did not induce IgA-specific helper activity when added to lymphocyte cultures alone but significantly enhanced IgA production when added with IL-4. It is concluded that IL-4 is the cytokine which specifically induce IgA in humans while IL-5 and TGF-beta show such activity in mice. Further sutdies are warranted to explore clinical significance of IL-4 and IL-6 in patients with IgA nephropathy.

众所周知，伊加肾病是由IgA主导的免疫复合物介导的，虽然诱导这种免疫复合物的发病机制是未知的，本研究的目的是阐明细胞因子是负责伊加肾病患者和他们的一些亲属中观察到的伊加的产生增加。对56例伊加肾病患者和96名家族成员进行了研究。54例健康成人作为对照组。分离外周血单个核细胞（PBMC），并通过免疫吸附技术浓缩富含B细胞的级分以及T α 4细胞（即伊加特异性辅助T细胞）。将白细胞介素4、5和6（IL-4、IL-5、IL-6）和组织生长因子（TGF-β）单独或以组合形式与这些B和T细胞培养物共培养。通过流式细胞术对这些培养物中的IgG、伊加和IgM携带细胞进行定量。用ELISA法检测IgG、伊加、IgM和IgE的浓度，在IL-5、IL-6和TGF-β的培养物中伊加的产生没有显著增加。然而，IL-4诱导IgA承载细胞和培养物中的上清液伊加显着增加与此细胞因子添加和不添加IL-6。IL-6不诱导IgA特异性辅助活性时，单独加入淋巴细胞培养物，但显着增强伊加的生产时，与IL-4。结论是IL-4是特异性诱导人伊加的细胞因子，而IL-5和TGF-β在小鼠中显示出这种活性。IL-4、IL-6在伊加肾病患者中的临床意义有待进一步研究。

项目成果

Yagame,M.,Suzuki,D.,Watanabe K.,Nakao,E,Eguchi,K,Miyazaki M.,Matsumoto,Y.,Yano N.Kuramoto T.,Sako,H.,Ashitate,M.and Suzuki,K: "Significance of levels of circulating IgA-class immune complexes in discriminont onalysis of patients with IgA nepmopathy before

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