供体特异性MICA抗体介导急性体液性排斥反应临床病理观察(附一例报道)

The clinical and pathologic character of donor special anti-MICA antibody induced acute humoral rejection

目的:观察供体特异性MICA抗体介导的急性体液性排斥反应(AHR)临床及病理改变特征。方法:回顾性分析1例接受肾移植的29岁年轻女性,术后出现肾功能减退,予移植肾活检明确诊断,在移植肾功能恢复后重复活检明确病理改变。术前及术后7d、1.5月、3次移植肾活检时(分别为术后12d、1月、4.5月)共6个时间点留取血样标本检测FLOW-PRA、MICA抗体、抗内皮细胞抗体(AECA)。同时检测供者、受者以及MICA抗体的基因分型。结果:6次血清标本中FLOW-PRA、AECA全部为阴性结果。术前及术后7d,第一次移植肾活检时患者MICA抗体为阴性。第二次移植肾活检时MICA抗体转为阳性。供体MICA基因型为MICA 002/02,MICA008,受者MICA基因型为MICA010,MICA010。MICA抗体基因分型提示为针对MICA02、MICA19、MICA07位点的抗体,受者体内存在针对供体的抗MICA02抗体。患者前二次移植肾活检组织学改变相同,符合AHR的特点。但免疫荧光证实第二次移植肾活检肾组织管周毛细血管C4d染色由阴性转为阳性。治疗上予甲基泼尼松龙(MP)冲击联合FK506+MMF+泼尼松+雷公藤多苷(TW)四联免疫抑制方案。第三次移植肾活检组织学基本正常,免疫荧光C4d染色由阳性转阴,最终患者排斥反应逆转,移植肾功能恢复正常。结论:肾移植术后受者体内可产生针对供体的特异性MICA抗体,该抗体可介导AHR。MP冲击治疗联合FK506+MMF+泼尼松+TW免疫抑制方案可逆转抗供体特异性MICA抗体介导的AHR。抗供体特异性MICA抗体介导的AHR的临床表现,病理特征及预后还有待进一步观察。

Objective：To observe the clinical and pathologic character of donor special anti-MICA antibody mediated acute humoral rejection, nethodology：A twenty-nine aged female patient who had quickly allograft disfunction after renal transplantation （RT） was studied retrospectively. She received three consecutive biopsies on 12th day, 30th day and 4. 5 month after RT. According to the protocol we collected the blood samples at pre-RT and 7th day, 1.5 month after RT, and before every biopsy for detecting her FLOW-PRA, AECA and anti-MICA antibody. The patients＇ MICA genotype and the anti-MICA antibody genotype were also detected at the same six time point. Results：The FLOW-PRA and AECA were negetive at the six time point. The anti-MICA antibody was also negetive at pre-RT, 7th day post-RT and before the first biopsy. While it turned to be positive before the second biopsy. The MICA genotype of donor was MICA002/02, MICA008, and the genotype of recipient was MICA010, MICA010. The genotype of anti-MICA antibody was to aim directly at MICA02, MICA19, and MICA07. The recipient had the donor special anti-MICA02 antibody. The first biopsy showed that the patient had untypical acute humoral rejection and CAd deposition was negative in peritubular capillary （PTC）. The second the patient had typical acute humoral rejection and C4d deposition was positive in PTC. The patient was administrated prednisotone pulse therapy combined with the immunosuppressive protocol including tacrolimus, MMF, prednisone and Tripterygium wilfordii （TW） , and her acute rejection was reversed. The level of serum creatinine decreased to normal range. The repeat renal biopsy showed no pathological features of acute humoral rejection, and CAd deposition in PTC turned to be negative. Conclusion：The donor special anti-MICA antibody could mediate acute humoral rejection. The regime of prednisolone pulse therapy combined with the immunosuppressive protocol （tacrolimus, MMF, prednisone and TW） could reverse the donor special anti-MICA antibody mediated acute humoral rejection.