幽门螺杆菌致IgA肾病的临床证据

发布时间：2018-03-16 06:04

本文选题：幽门螺杆菌感染　切入点：IgA肾病　出处：《四川医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:Ig A肾病是全球范围内最常见的原发性肾小球疾病,在我国已成为导致慢性肾功能衰竭最主要的肾小球疾病,大约30%~50%的患者在疾病诊断后20年内发展到终末期肾衰竭(ESRD);目前,幽门螺杆菌(Hp)感染备受关注,已有研究提示Hp感染可能与Ig A肾病发病有关。我们前期体外研究证实幽门螺旋杆菌感染或毒力因子Cag A可通过刺激B淋巴细胞增殖、影响Ig A1分泌以及低糖基化参与Ig A肾病的发生,但是尚缺乏临床证据。本研究拟通过检测Ig A肾病患者Hp感染情况,研究分析Hp感染与Ig AN临床预后之间的关系,并检测Hp感染对Ig A肾病患者Ig A1的产生、Ig A1糖基化的影响以及肾组织中Hp抗原和Cag A的沉积情况,寻找Hp参与Ig A肾病的临床证据。方法:收集经肾病理活检确诊为原发性肾小球疾病患者42例,排除继发性肾病,包括Ig A肾病患者22例和非Ig AN的原发性肾小球疾病患者20例,采用14C-尿素呼气试验、酶联免疫吸附法(ELISA)检测Hp感染情况,酶联免疫吸附法(ELISA)法检测血清中Ig A1浓度,HAA凝集素结合试验法检测Ig A1低糖基化程度,运用免疫组织化学方法检测肾组织中Hp抗原及Cag A沉积情况,同时收集患者临床资料、血Ig A、补体C3、血肌酐、24h尿蛋白定量、估算肾小球滤过率、病理指标结果。结果:1、14C-尿素呼气实验结果显示,Ig AN患者Hp现症感染率与n-Ig AN患者及健康人无明显差异;但ELISA结果显示Ig AN患者血清Hp-Ig G抗体的阳性率显著高于n-Ig AN患者及健康人(P0.05)。2、Ig AN患者中,Hp阳性患者血清Ig A1分子浓度及其与HAA凝集素的结合能力均高于Hp阴性患者。3、Ig AN患者中,Hp感染阳性患者与Hp感染阴性患者相比,血Ig A及Ig A/C3比值增高,24h尿蛋白低及估算肾小球滤过率降低。4、Hp抗原及Cag A均在肾小管沉积,且沉积部位一致,而在肾小球部位无阳性发现。Ig AN患者肾组织Hp抗原及Cag A沉积程度显著高于n-Ig AN患者。Ig AN患者中,Hp感染阳性患者肾组织中Hp及Cag A沉积阳性率显著高于Hp感染阴性患者。而n-Ig AN患者中,Hp感染阳性患者与Hp感染阴性患者无差异。结论:Ig AN患者与n-Ig AN患者及健康人Hp现症感染率相似。幽门螺旋杆菌通过诱导强烈免疫反应,使Ig AN患者体内针对Hp感染的抗体显著增加,促进机体Ig A1分泌以及低糖基化,并加重肾功能损害。Hp抗原及Cag A均在肾组织的肾小管部位沉积,且Ig AN患者肾组织Hp抗原及Cag A沉积程度显著增高;Hp感染可显著增加Ig AN患者肾组织中Hp抗原及Cag A沉积机会。研究提示幽门螺旋杆菌感染可能在Ig A肾病的发病机制中起到直接的病理作用,其机制可能与介导肾小管损伤相关,清除幽门螺杆菌可能有助于幽门螺杆菌感染阳性的Ig A肾病患者的治疗。
[Abstract]:Objective: IgA nephropathy is the most common primary glomerular disease in the world, and it has become the most important glomerular disease leading to chronic renal failure in China. About 30 percent of patients develop end stage renal failure within 20 years of diagnosis; currently, Helicobacter pylori (HP) infection is a major concern. Previous studies have shown that HP infection may be related to the pathogenesis of IgA nephropathy. Our previous studies in vitro have demonstrated that Helicobacter pylori infection or virulence factor Cag A can stimulate B lymphocyte proliferation. The effect of Ig A1 secretion and low glycosylation on the pathogenesis of IgA nephropathy, but there is still no clinical evidence. This study is to study the relationship between HP infection and clinical prognosis of IgA nephropathy patients by detecting HP infection in patients with IgA nephropathy, and analyzing the relationship between HP infection and clinical prognosis of IgA nephropathy. The effect of HP infection on the production of IgA1 in patients with IgA nephropathy and the deposition of HP antigen and Cag A in renal tissue were detected. Methods: 42 cases of primary glomerular disease diagnosed by biopsy of nephropathy were collected to exclude secondary nephropathy. 22 patients with IgA nephropathy and 20 patients with non-IgAN primary glomerular disease were tested for HP infection by 14C- urea breath test and Elisa. Enzyme linked immunosorbent assay (Elisa) was used to detect the concentration of IgA1 in serum and the level of low glycosylation of IgA1 was detected by HAA agglutinin binding assay. HP antigen and Cag A deposition in renal tissue were detected by immunohistochemical method. The clinical data of the patients were collected at the same time. Serum IgA, complement C3, serum creatinine, 24 hours urinary protein, glomerular filtration rate and pathological index were estimated. Results the HP infection rate of patients with Ig an was not significantly different from that of n-Ig an patients and healthy persons. The results of ELISA showed that the positive rate of serum Hp-Ig G antibody in patients with IgAN was significantly higher than that in patients with n-Ig an and healthy controls. The concentration of IgA1 and its binding ability with HAA agglutinin in patients with HP positive were higher than those in patients with HP negative. (3) HP infection positive patients in Ig an patients were compared with those with HP negative infection. The increase of serum IgA and IgA / C3 ratio and the decrease of 24 hours urinary protein and the decrease of estimated glomerular filtration rate. 4 HP antigen and Cag A were deposited in renal tubules, and the deposition site was the same. However, there was no positive rate of HP and Cag A deposition in renal tissue in patients with IgAN and n-IgAN patients. The positive rates of HP and Cag A in renal tissues of patients with Hp-positive infection were significantly higher than those of patients with HP infection in n-IgAN patients. There was no difference between the patients with positive HP infection and those with negative HP infection in n-Ig an patients. Conclusion the infection rate of HP in patients with 1% Ig an is similar to that in patients with n-Ig an and healthy people. Helicobacter pylori induces strong immune response. The antibody against HP infection was significantly increased in IgAN patients, which promoted the secretion of IgA1 and low glycosylation, and aggravated the renal function damage. HP antigen and Cag A were deposited in the renal tubules of renal tissue. HP antigen and Cag A deposition in renal tissue of patients with IgAN increased significantly. HP infection in renal tissue of IgAN patients increased the chances of HP antigen and Cag A deposition in renal tissue of IgAN patients. It is suggested that Helicobacter pylori infection may occur in IgA nephropathy. Play a direct pathological role in the pathogenesis of the disease, The mechanism may be related to mediated renal tubular injury and the clearance of Helicobacter pylori may contribute to the treatment of patients with HP positive IgA nephropathy.
【学位授予单位】：四川医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R692.31

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