肾移植后抗体介导的排斥反应的临床病理特征及个体化免疫治疗研究

摘要

目的：探讨肾移植后抗体介导的排斥反应（AMR）的临床病理特征与个体化免疫治疗策略及预后。方法回顾性分析2010年1月至2013年12月，在河南中医学院第一附属医院泌尿外科肾移植科收治的32例肾移植术后经病理确诊的 AMR 患者的临床资料。根据不同患者的临床病理特点，采取相应的免疫干预措施，分别于治疗前及治疗后测定肾功能、群体反应性抗体（PRA）及血清免疫球蛋白（Ig）G、IgA、IgM水平，并观察不良反应。结果本组患者中急性抗体介导的排斥反应（AAMR）18例，慢性抗体介导的排斥反应（CAMR）14例；PRA 阳性患者13例，其中 8例 （62％，8／13）为供体特异性抗体，5例（38％，5／13）为非供体特异性抗体。早期 AAMR 的主要病理表现为急性肾小管坏死（ATN）样改变，管周毛细血管炎及小球炎，动脉纤维素样坏死，C4d 在肾小管周围毛细血管（PTC）呈线性沉积，免疫球蛋白或 C3在动脉壁沉积。CAMR 的病理表现为肾小球病样改变，PTC 基底膜分层，动脉内膜纤维增厚，C4d 在 PTC 弥漫沉积。经治疗，肾功能恢复正常20例（63％，20／32），肾功能稳定7例（22％，7／32），血清肌酐（Scr）呈缓慢升高 5例（16％，5／32），其中 2例 （2／5）回归血液透析，3例 （3／5）尚不需透析治疗，无1例死亡。治疗后血尿素氮（BUN）、Scr、PRA 及血清 IgG、IgA、IgM较治疗前明显降低（均为 P ＜0.01）。治疗期间未见严重不良反应。结论肾移植术后 AMR 可表现为 AAMR 或 CAMR。AMR 诊断的金标准是移植肾病理活组织检查，治疗 AMR 的关键措施是及时采取有效的个体化免疫治疗方案。%Objective To investigate clinicopathologic characteristics,individualized immunotherapy and prognosis of antibody-mediated rejection (AMR)after renal transplantation.Methods Clinical data of 32 patients,who were confirmed as AMR after renal transplantation by pathology and admitted in the Department of Urology and Renal Transplantation of the First Affiliated Hospital of Henan Traditional Medical College from January 2010 to December 2013,were retrospectively studied.The corresponding immunological intervention was adopted according to the clinicopathologic characteristics of different patients.The indicators including renal function,panel reactive antibody (PRA)and serum immunoglobulin (Ig)G,IgA and IgM level before and after treatment were determined,and adverse reactions were observed.Results Of all 32 patients, 18 developed acute antibody-mediated rejection (AAMR ) and 14 developed chronic antibody-mediated rejection (CAMR).Of 13 PRA-positive patients,8 (62%,8 /13)cases were with donor specific antibody and 5 (38%,5 /13)cases were with non-donor specific antibody.The primary pathological manifestations of early AAMR were changes of acute tubular necrosis (ATN ),peritubular capillary inflammation,glomerulitis, fibrinoid necrosis of small arteries,linear C4d deposition in peritubular capillaries (PTC)and immunoglobulin or C3 deposition in arterial wall.The pathological manifestations of CAMR were changes of glomerulopathy, splitting of PTC basement membrane,fibrous intimal thickening and diffuse C4d deposition in PTC.After treatment,the renal function of 20 (63%,20 /32)patients returned to normal,the renal function of 7 (22%, 7 /32)patients were stable,the serum creatinine (Scr)of 5 (16%,5 /32)patients increased slowly.Of such 5 patients,2 (2 /5 )patients continued hemodialysis,3 (3 /5 )patients did not need hemodialysis and no patient died.The indicators including blood urea nitrogen (BUN),Scr,PRA and serum IgG,IgA and IgM after treatment decreased significantly when compared with those before treatment (all in P <0.01).No serious adverse reaction was noted during the treatment.Conclusions AMR may manifest as AAMR or CAMR after renal transplantation.The gold standard for diagnosing AMR is pathologic biopsy of transplant kidney.To adopt effective individualized immunotherapy in time is the critical measure for treatment of AMR.