PLA2R及其抗体在特发性膜性肾病中的临床诊疗价值

发布时间：2018-04-02 09:38

本文选题：特发性膜性肾病　切入点：M型磷脂酶A2受体　出处：《青岛大学》2017年硕士论文

【摘要】：研究目的:特发性膜性肾病(IMN)是一组以肾病综合征为主要临床表现、以肾小球基底膜受损为主要病理特征的,好发于40~50岁人群的肾小球疾病。近年来学者们研究发现约有74%的IMN患者肾组织可检测到M型磷脂酶A2受体(M-type phospholipase A2 receptor,PLA2R),并且发现了相应的抗体,然而两者如何参与IMN的发病机制尚不明确。本研究目的是探讨两者在IMN中表达的相关性以及两者与IMN的诊断、疾病活动、预后的关系。研究方法:1.选取2016年3月至2016年12月收治于青岛大学附属医院肾病科并行肾穿刺活检后确诊为IMN的36例患者作为观察组,微小病变肾病、狼疮性肾炎、Ig A肾病等非IMN的其他肾小球疾病共14例作为对照组,分析两组间一般临床资料以及白蛋白水平、24小时尿蛋白定量、血肌酐等可反映肾脏受损程度的指标的差异。2.使用免疫组织化学染色法检测两组患者肾组织PLA2R的表达,使用ELISA法检测血清抗PLA2R抗体的滴度,计算两者在不同组的阳性率,并在IMN组中分析两者的相关性。3.使用SPSS统计软件制作受试者工作特征曲线(ROC),分析PLA2R及其抗体对IMN诊断的准确性。4.分别在IMN组中分析PLA2R以及其抗体的阳性表达与肾脏受损程度的关系。5.在PLA2R全部为阳性的IMN患者中,分抗体阳性组与阴性组,并比较两组间肾脏受损程度的不同。6.分析IMN组中抗体滴度与疾病活动水平的关系。7.收集治疗时间超过3个月的IMN组的33例患者的随访资料,分析PLA2R以及其抗体与预后的关系。研究结果:IMN组与对照组间发病年龄、性别、血压、24小时尿蛋白定量、血清白蛋白、血清肌酐等指标均无显著性差异(p0.05),肾组织PLA2R及其抗体的阳性检出均有统计学差异。1.PLA2R诊断IMN的灵敏度是75.00%,特异度是85.71%;PLA2R抗体诊断IMN的灵敏度是63.89%,特异度是92.86%;PLA2R联合抗体诊断IMN的灵敏度是75.00%,特异度是78.57%。2.PLA2R抗体曲线下面积(AUCROC)是0.784,肾组织PLA2R的AUCROC是0.875。3.IMN组中血清PLA2R抗体阳性与阴性患者的血清肌酐间的差异无统计学意义(p0.05),24小时尿蛋白定量分别是5.56±2.80 g/24h和3.79±1.04 g/24h(p=0.011),血清白蛋白分别是21.23±4.79 g/L和24.41±3.83 g/L(p=0.037),均有显著性差异;IMN组中肾组织PLA2R阳性组与阴性组的肌酐、24小时尿蛋白定量、血清白蛋白均无显著性差异。4.PLA2R全部阳性的IMN患者中,抗体阳性组与阴性组间的肌酐、白蛋白、24小时尿蛋白定量均无显著性差异。5.IMN中患者抗体滴度与其24小时尿蛋白定量呈正相关(r=0.874,p0.001),与血清白蛋白水平呈负相关(r=-0.779,p0.001)。6.经免疫抑制治疗3个月后,肾组织PLA2R阳性组与阴性组的缓解率分别是41.7%和66.7%,用Fisher确切概率法计算其p0.05,无显著性差异;抗体阳性组与阴性组的缓解率分别是33.3%和75%,用Fisher确切概率法计算其p=0.025,PLA2R抗体阴性组的缓解情况优于PLA2R抗体阳性组。研究结论:肾组织PLA2R及其血清抗体在IMN中的表达并不完全一致,肾组织PLA2R阳性表达的患者,其抗体可为阴性。肾组织PLA2R及其抗体对IMN的诊断具有良好的灵敏度和特异度,有较高的疾病诊断价值。PLA2R与IMN疾病程度无相关性,PLA2R抗体的表达可反应肾脏损伤程度。另外,抗体滴度与尿蛋白定量及血白蛋白水平呈线性关系。IMN中抗体阳性的患者治疗的反应均不如阴性患者。
[Abstract]:Objective: idiopathic membranous nephropathy (IMN) is a group of nephrotic syndrome is the main clinical manifestation, glomerular basement membrane damage is the main pathological features, good hair at 40~50 year old population of glomerular diseases. In recent years many scholars have found that about 74% of the renal tissue of patients with IMN can be detected by M phospholipase A2 receptor (M-type phospholipase A2 receptor, PLA2R), and found the corresponding antibody, however the pathogenesis of both how to participate in IMN is not clear. The purpose of this study is to investigate the correlation between the expression of diagnosis, both in IMN and the two with IMN disease activity, the relationship between the prognosis. Methods: from March 2016 to 1. from December 2016 to the concurrent Department of nephropathy of Affiliated Hospital of Qiingdao University after the renal biopsy, 36 cases were diagnosed as IMN patients as the observation group, nephropathy, lupus nephritis, nephropathy and other non Ig A IMN other glomerular diseases A total of 14 cases as control group, analysis of two groups of general clinical data and serum albumin levels, 24 hour urinary protein quantitative immunohistochemical staining method was used to detect the expression of PLA2R in renal tissue of two patients with different.2. blood creatinine can reflect the degree of kidney damage index, titer of anti PLA2R antibody in serum was detected by ELISA. The positive rate calculated in different groups, and in IMN group the correlation analysis of.3. using the SPSS statistical software to make the receiver operating characteristic curve (ROC) analysis, PLA2R and its antibody on the diagnostic accuracy of.4. IMN respectively in the IMN group and the relationship between the positive expression of.5. PLA2R analysis of the antibody and the degree of kidney damage. In all PLA2R positive IMN patients, divided into positive group and negative group, and compared between the two groups of different.6..7. relationship between the kidney damage group IMN antibodies and the disease activity level analysis degree Collect the treatment time more than 3 months IMN group of 33 patients with follow-up data, analysis of PLA2R and its relationship with prognosis. Antibody results: IMN group and control group, age, gender, blood pressure, 24 hour urinary protein, serum albumin, and there were no significant differences in serum creatinine (P0.05), and PLA2R antibody positive detection sensitivity of renal tissue were statistically significant.1.PLA2R in the diagnosis of IMN was 75%, the specificity was 85.71%; the sensitivity of PLA2R antibody in the diagnosis of IMN was 63.89%, the specificity was 92.86%; PLA2R combined with IMN antibody diagnostic sensitivity was 75%, specificity of 78.57%.2.PLA2R antibody under the curve area (AUCROC) is in 0.784, PLA2R in renal tissue AUCROC is no statistically significant difference in serum creatinine in 0.875.3.IMN group serum PLA2R antibody positive and negative patients between (P0.05), 24 hour urinary protein quantitative difference is 5.56 + 2.80 g/24h and 3.79 1.04 g/24h (p=0.011), serum albumin were 21.23 + 4.79 and 24.41 + 3.83 g/L g/L (p=0.037), there were significant differences in renal tissue in the IMN group; PLA2R positive group and negative group serum creatinine, urine protein in 24 hours, there were no significant differences in serum albumin.4.PLA2R positive IMN patients, creatinine, antibody positive group and negative group of albumin, there were no significant differences between the 24 hour urinary protein quantitative.5.IMN in patients with antibody titers and 24 hours urine protein was positively correlated (r=0.874, p0.001), and negatively correlated with serum albumin level (r=-0.779, p0.001).6. after immunosuppressive therapy after 3 months renal tissue PLA2R positive group and negative group remission rate were 41.7% and 66.7%, calculate the P0.05 Fisher exact method, no significant difference; positive group and negative group remission rates were 33.3% and 75%, Fisher's exact test was used to calculate the P=0.025, relief is better than that of the PLA2R antibody positive group PLA2R antibody negative group. Conclusion: the expression of PLA2R in renal tissue and serum antibody in IMN is not exactly the same, the positive expression of PLA2R in renal tissue of patients, the antibody was negative. Has good sensitivity and specificity in the diagnosis of PLA2R and antibody in kidney tissue of the IMN. Have a higher disease diagnosis value of.PLA2R and IMN had no correlation with the extent of the disease, the expression of PLA2R antibody can reflect the degree of renal damage. In addition, albumin level and the titer of urinary protein and serum antibody showed a linear relationship between.IMN antibodies in patients with positive response to treatment were better than negative patients.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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