自身抗体在特发性膜性肾病病情评估中的作用

发布时间：2018-06-15 17:56

本文选题：特发性膜性肾病 + 磷脂酶A2受体　；参考：《山东大学》2017年硕士论文

【摘要】：特发性膜性肾病(IMN)是成人肾病综合征的最常见原因之一,占所有肾穿刺病理类型的30%左右[1],近几年IMN占原发性肾小球疾病的比重有持续升高的趋势。在IMN成人患者的血清中检测到抗M型磷脂酶A2受体(PLA2R)的抗体,在继发性膜性肾病和其他肾小球疾病患者中血清抗PLA2R抗体却鲜有发现,证明PLA2R或许成为成年人IMN的致病特异性抗原,而抗PLA2R抗体可能具有诊断意义的血清标志物[2,3]。足细胞是肾小球滤过屏障的重要组成部分。现有观点普遍认为,循环抗体与足细胞固有抗原原位免疫复合物在足细胞下的沉积是IMN发病的始动环节[1]。2009年,Beck等[5]发表在《New England Journal of Medicine》的文章中首次发现位于人类足细胞膜上的M型磷脂酶A2受体(M-type phospholipase A2 receptor,PLA2R)为IMN的特异性靶抗原,研究发现高达70%IMN患者血清抗PLA2R自身抗体(anti-PLA2R)阳性,并与PLA2R特异性结合于足细胞下形成颗粒状免疫复合物,而继发性肾小球疾病却鲜有检出,这提示anti-PLA2R为IMN所特有的抗体。近期有学者研究醛糖还原酶(AR)和超氧化物歧化酶(SOD2)可能成为IMN的相关致病因素。2010年,Marco Prunotto[6]等应用蛋白质组学的方法在膜性肾病患者血清及肾组织中均发现了足细胞抗原AR及SOD2产生的相应抗体,且他们都能与特异性循环抗体结合并表达,同时在肾小球上皮下免疫沉积。由此猜测SOD2足细胞作为致病因子参与了 IMN的疾病过程中的可能性。目前对于膜性肾病的临床治疗应用免疫抑制剂的时间、方式及停药时机仍有争议,如何能在免疫抑制剂毒副反应最小的前提下发挥其最大疗效是研究的热点问题。临床推荐首选的治疗方案为激素联合环磷酰胺,替代方案为小剂量激素联合他克莫司或环孢素A。明确不同治疗方案对特发性膜性肾病患者的临床疗效、毒副作用和远期预后,有助于临床医生根据患者的不同情况选择相适宜的治疗手段。目的:为探讨特发性膜性肾病(IMN)患者血清中抗磷脂酶A2受体(PLA2R)、抗醛糖还原酶(AR)和抗超氧化物歧化酶(SOD2)抗体水平动态变化与病情的关系。比较激素联合环磷酰胺与激素与他克莫司联用两种不同治疗方案对自身抗体滴度变化影响的异同。方法:56例临床及肾穿刺病理诊断为IMN的患者为研究对象,在治疗前、治疗后1、3、6、9、12个月抽自凝血,采用酶联免疫吸附法检测血清抗PLA2R抗体、抗醛糖还原酶(AR)抗体和抗超氧化物歧化酶(SOD2)抗体,同时检测尿蛋白定量及其他血生化指标等。结果:治疗前患者血清PLA2R抗体阳性者占70.59%。在观察期内,尿蛋白定量随着PLA2R抗体滴度降低而逐渐降低,而同时血清白蛋白水平逐渐升高。在治疗后平均5个月后尿蛋白均显著降低,血浆白蛋白水平升高,其中环磷酰胺组12例达到完全缓解,20例部分缓解,未缓解4例;他克莫司组完全缓解为4例,16例部分缓解。两治疗组患者缓解情况的差异无统计学意义(p0.05)。血清抗AR抗体阳性率46.42%,其抗体滴度仅与eGFR呈正相关关系。抗SOD2抗体阳性率为67.8%,其滴度与各项生化指标无明显相关关系。结论:1.抗PLA2R抗体是特发性膜性肾病的特异性自身抗体;2.两种治疗治疗方案对于IMN患者病情缓解无明显差异性;3.IMN患者的血清抗PLA2R抗体水平与疾病严重程度密切相关,而血清抗AR抗体和抗SOD抗体与IMN病情变化无显著相关。
[Abstract]:Idiopathic membranous nephropathy (IMN) is one of the most common causes of adult nephrotic syndrome, which accounts for about 30% [1] of all renal pathological types. In recent years, the proportion of IMN in primary glomerular disease has continued to rise. In the serum of IMN adult patients, antibodies against M phosphatidase A2 receptor (PLA2R) are detected and in secondary membranous nephropathy. Serum anti PLA2R antibodies in patients with other glomerular diseases are rarely found, suggesting that PLA2R may become a specific antigen of adult IMN, and anti PLA2R antibodies may be a diagnostic serum marker, [2,3]. podocyte is an important part of the glomerular filtration barrier. Current views are generally believed that circulating antibodies and podocytes are generally believed. The deposition of the intrinsic antigen in situ complexes under the podocyte is the beginning of the onset of IMN [1].2009. Beck and other [5] published in the article for the first time found the specific target antigen of the M type phospholipase receptor on the human foot cell membrane. It was found that the serum anti PLA2R autoantibody (anti-PLA2R) of the patients with high 70%IMN was positive, and the PLA2R specificity was associated with the formation of granular immune complex under the podocyte, and the secondary glomerular disease was rarely detected. This suggests that anti-PLA2R is a specific antibody to IMN. Recently, some scholars have studied aldose reductase (AR) and superoxide dismutase (SOD2). The associated pathogenic factors of IMN may be.2010 years, and the method of proteomics, such as Marco Prunotto[6], found the corresponding antibodies produced by the podocyte antigen AR and SOD2 in the serum and renal tissues of patients with membranous nephropathy, and they can be combined with specific circulating antibodies and expressed in the glomerulus. The possibility of measuring SOD2 podocyte as a pathogenic factor is involved in the disease process of IMN. The time, way and time for the application of immunosuppressive agents for the clinical treatment of membranous nephropathy are still controversial. How to play its most important effect on the premise of minimal side reaction of immunosuppressant is a hot issue. Clinical recommendation The first choice is hormone combined with cyclophosphamide, and the alternative regimen for small dose hormone combined with tacrolimus or cyclosporin A. is a clear and different treatment for patients with idiopathic membranous nephropathy. The clinical efficacy, side effects and long-term prognosis of the treatment are helpful for clinicians to choose appropriate treatment according to the patient's different conditions. To investigate the relationship between the dynamic changes of serum anti phospholipase A2 receptor (PLA2R), anti aldose reductase (AR) and anti superoxide dismutase (SOD2) antibody in patients with idiopathic membranous nephropathy (IMN), and to compare the differences and similarities between two different treatments of hormone combined with cyclophosphamide and corticosteroid and tacrolimus. Methods: 56 patients with IMN in clinical and renal biopsy were studied. Before treatment, 1,3,6,9,12 months after treatment were taken from blood coagulation, enzyme linked immunosorbent assay was used to detect serum anti PLA2R antibody, anti aldose reductase (AR) antibody and anti superoxide dismutase (SOD2) antibody, and urine protein quantitative and other biochemical indexes were detected at the same time. Results: in the observation period, the serum PLA2R antibody positive in the patients with 70.59%. was decreased with the decrease of the PLA2R antibody titer, while the level of serum albumin increased at the same time. After 5 months of treatment, the urine protein decreased significantly and the plasma white egg white level increased, of which 12 cases of cyclophosphamide group reached the end. Total remission, 20 cases of partial remission, 4 cases without remission, 4 cases of complete remission in the tacrolimus group and 16 cases of partial remission. The difference of remission in two treatment groups was not statistically significant (P0.05). The positive rate of anti AR antibody in serum was 46.42%, the titer of antibody was only positively correlated with eGFR. The positive rate of anti SOD2 antibody was 67.8%, its titer and various biochemical indexes. Conclusion: 1. anti PLA2R antibodies are specific autoantibodies in idiopathic membranous nephropathy, and there is no significant difference between the 2. and two treatments for the remission of IMN patients. The serum anti PLA2R antibody level of 3.IMN patients is closely related to the severity of the disease, but there is no significant difference between the serum anti AR and the SOD antibody and the IMN condition. It's related.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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