肾移植术后BK病毒感染：危险因素及免疫组织化学因素与BK病毒相关件肾病进展的免疫组织化学因素相关分析

发布时间：2018-05-02 03:48

  本文选题：肾移植 + BK病毒　； 参考：《南京大学》2017年硕士论文

【摘要】：肾移植术后BK病毒感染及危险因素分析目的:研究国内肾移植术后BK病毒(BK virus,BKV)感染情况,分析肾移植术后BKV感染的危险因素。方法:选取2015年6月—2016年7月于南京军区南京总医院常规接受血、尿液BKV DNA检测的肾移植术后受者作为研究对象,并将同时期接受检测的尿毒症透析患者、健康活体供者作为对照组。了解肾移植术后BKV感染情况,探讨肾移植受者的一般情况、术后并发症及免疫抑制剂方案等因素对BKV感染是否有影响。结果:肾移植术后受者的尿液BKVDNA阳性率为19.9%,其中同时伴有血液BKVDNA阳性的发生率为1.3%,而尿毒症透析患者、健康活体供者的尿液BKV DNA阳性率分别为6.3%、4.2%,后两组患者的血液BKV DNA均阴性。肾移植术后受者的尿液BKV DNA阳性率较尿毒症透析患者、健康活体供者增加(P0.001),而尿毒症透析患者、健康活体供者的尿液BKVDNA阳性率相似(P=0.842)。单因素分析显示:术后肺部感染、急性排斥反应及术后服用他克莫司(Tacrolimus,FK506)与肾移植术后BKV感染相关(P0.05),而受者的性别、年龄、并发糖尿病、移植肾延迟肾功能恢复(delayed recovery of graft function,DGF)及术后服用环孢霉素A(Cyclosporine,CsA)、吗替麦考酚酸酯(Mycophenolate Mofetil,MMF)与BKV感染均无相关性('P0.05);进一步行多因素分析显示:术后肺部感染(OR[95%CI],3.468[1.227-9.802];P=0.019)、急性排斥反应(OR[95%CI],2.645[1.142-6.127];P =0.023)、术后服用 FK506(OR[95%CI],2.408[1.104-5.254];P-0.027)仍与肾移植术后BKV感染相关。结论:肾移植术后BKV感染的发生率明显增加。术后肺部感染、急性排斥反应及应用以FK506为主的免疫抑制剂方案均可增加肾移植术后BKV感染的风险。影响BK病毒相关性肾病进展的相关免疫组织化学因素分析目的:观察肾移植术后BK病毒相关性肾病(BK virus associated renal allograft nephropathy,BKVAN)患者不同阶段免疫组织化学因素的变化情况,探讨其临床意义。方法:选取南京军区南京总医院经病理明确诊断为BKVAN的53例患者。根据第3版美国移植协会感染诊疗指南,将BKVAN患者分为轻度12例(Stage A)、中度22例(Stage B)、重度19例(Stage C),比较3组BKVAN患者移植肾组织中CD4+、CD8+、CD20+、CD138+、CD68+细胞,白细胞介素2受体(IL-2R)及肾小管上皮细胞HLA-DR的阳性表达变化情况。结果:BKVAN 患者肾组织中 CD4+、CD8+、CD20+、CD138+、CD68+细胞、IL-2R和肾小管上皮细胞HLA-DR均有阳性表达,且随着BKVAN患者的病程进展,上述浸润细胞的表达有增加趋势。其中,重度组与轻度组相比CD4+、CD20+、CD138+、CD68+细胞的浸润具有显著统计学差异(P0.01),而三组间CD8+细胞、IL-2R和肾小管上皮细胞HLA-DR的阳性表达均无统计学差异。结论:BKV诱发肾组织中T淋巴细胞、B淋巴细胞及单核巨噬细胞免疫系统的活化,其中移植肾组织中CD4+、CD20+、CD138+及CD68+细胞的显著增加是造成BKVAN进行性加重的主要因素。
[Abstract]:Analysis of BK virus infection and risk factors after renal transplantation objective: to study the BK virus BK virus BKV infection after renal transplantation in China and to analyze the risk factors of BK virus infection after renal transplantation. Methods: renal transplant recipients who received blood and urine BKV DNA from June 2015 to July 2016 in Nanjing General Hospital of Nanjing military region were selected as the study subjects, and the uremic dialysis patients who were tested at the same time were selected. Healthy living donors served as control group. To investigate the infection of BKV after renal transplantation, to explore the general situation of renal transplant recipients, postoperative complications and immunosuppressive regimen, and other factors affecting BKV infection. Results: the positive rate of urine BKVDNA was 19.9 in recipients of renal transplantation, and the incidence of positive BKVDNA in blood was 1.3. The positive rate of urine BKV DNA in uremic dialysis patients and healthy living donors was 6.30.The BKV DNA in blood of the latter two groups was negative. The positive rate of urine BKV DNA in recipients after renal transplantation was higher than that in uremic dialysis patients, and the positive rate of urine BKVDNA in healthy donors was similar to that in uremic dialysis patients. Univariate analysis showed that postoperative pulmonary infection, acute rejection and tacrolimus FK506) were associated with BKV infection after renal transplantation (P 0.05), and the recipients had sex, age, and diabetes mellitus. Delayed renal function recovery and postoperative administration of cyclosporine, mycophenolate mofetil (MMF) were not associated with BKV infection. Further multivariate analysis showed that OR [95%CI] 3.468 [1.227-9.802], acute rejection OR [95%CI] 2.645 [1.142-6.127] P FK506(OR [95%CI] 2.408 [1.104-5.254] P-0.027 was still associated with BKV infection after renal transplantation. Conclusion: the incidence of BKV infection increased significantly after renal transplantation. Postoperative pulmonary infection, acute rejection and the use of immunosuppressant regimen based on FK506 can increase the risk of BKV infection after renal transplantation. Analysis of immunocytochemical factors affecting the progression of BK virus associated nephropathy objective: to observe the changes of immunocytochemical factors in patients with BK virus associated renal allograft nephropathy after renal transplantation and to explore its clinical significance. Methods: 53 patients with BKVAN diagnosed by pathology in Nanjing General Hospital of Nanjing military region were selected. According to the third edition of the American Transplantation Association guidelines for the diagnosis and treatment of infection, the patients with BKVAN were divided into three groups: mild 12 cases with stage A, moderate 22 cases with stage BV, severe 19 cases with stage C, and compared the CD138 CD68 cells of CD4 CD8 + CD20 and CD138 in three groups of patients with BKVAN. The positive expression of IL 2 receptor IL 2 R) and HLA-DR in renal tubular epithelial cells. Results the positive expression of IL-2R and HLA-DR in the renal tissue of CD4 / CD8 / CD20 / CD138 / CD138 / CD138 / CD68 was observed in the patients with BKVAN. The expression of the above infiltrating cells tended to increase with the progression of the disease course of BKVAN. There was significant difference in the infiltration of CD4 CD20 CD138 and CD68 cells between the severe group and the mild group (P 0.01), but there was no significant difference in the expression of IL-2R in CD8 cells and HLA-DR expression in renal tubular epithelial cells among the three groups. Conclusion the activation of T lymphocyte B lymphocytes and mononuclear macrophage immune system was induced by BKV. The significant increase of CD4 CD20 CD138 and CD68 cells was the main factor that caused the progressive aggravation of BKVAN.
【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R699.2
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本文编号：1832249