Study of pathogenesis of IgA nephropathy

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）。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。这些报道加强了粘膜免疫与IgAN发病机制之间关系的可能性。然而，试图在IgAN患者中分离特异性伊加循环免疫复合物相关抗原的尝试并不成功。我们已经表明，粘膜感染如咽炎通常与IgAN的急性发作有关。一种免疫复合物疾病，由于病人长期暴露于环境抗原而引起粘膜免疫反应不良。我们之前已经观察到， ...更多信息 副流感嗜血杆菌（HP）通常从IgAN患者的咽部分离，而不是从其他疾病患者的咽部分离。我们还发现，在IgAN患者中，HP抗原外膜（OMHP）的肾小球沉积和抗OMHP的IgA-Ab血清浓度增加。此外，我们还表明，IgAN患者通过抗OMHP的多克隆活化，特异性地增加了抗OMHP的IgA-Ab的产生，并从一种同种型转换为另一种同种型，例如从IgM转换为伊加，本研究旨在通过检测IgAN及其他肾小球疾病（OGD）患者扁桃体中OMHP与淋巴细胞的胸腺嘧啶核苷（TdR）摄取，探讨OMHP与淋巴细胞之间的免疫反应。IgAN患者的刺激指数（OMHP刺激的淋巴细胞摄取^3 H-TdR（cpm）/未刺激的淋巴细胞摄取^3 H-TdR（cpm））显著高于OGD患者，提示OMHP与扁桃体淋巴细胞之间的免疫应答在IgAN的发病中起作用。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. Thus, the Ab is probably produced as part of the specific host immune response to various environmental antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgAN.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 byb a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haem … More ophilus 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 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 productiion 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 significant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN.Our objective was to clarify the immune response between OMHP and lymphocytes in tonsils from patients with IgAN or other glomerular diseases (OGDs) by measuring thymidine uptake. Patients with IgAN showed a significantly higher level of stimulation index (^3H-thymidine uptake by the stimulated lymphocytes by OMHP (cpm)/^3H-thymidine uptake by the unstimulated lymphocytes (cpm) than did patients with OGDs.These results suggest that the immune response between OMHP and lymphocytes in tonsils play a role in pathogenesis of IgAN. Less