肾移植术后新发供者特异性抗体对受者预后影响的回顾性研究

De novo donor specific antibody affect the prognosis of kidney transplant recipients: retrospective study

目的探讨肾移植术后新发供者特异性抗体(dnDSA)阳性率与HLA错配位点的关系,并探究dnDSA对移植肾长期存活及排斥反应发生的影响。方法回顾性队列研究101例肾移植受者的病例资料,按抗HLA抗体和dnDSA检测情况将受者分成三组,分别为抗HLA抗体阴性组(HLA-组)70例,抗HLA抗体阳性dnDSA阴性组(dnDSA-组)23例,以及抗HLA抗体阳性dnDSA阳性组(dnDSA^+组)8例,记录受者移植后排斥反应发生情况和移植物长期存活情况,评估dnDSA对排斥反应发生率和存活率的影响,同时观察发生排斥反应时各组移植肾病理表现的差异。结果dnDSA+组HLA-A、B和HLA-DR位点的错配数均显著多于HLA^-组和dnDSA^-组(P=0.047,P=0.010);dnDSA+组移植物存活率显著低于HLA^-组和dnDSA^-组(P=0.001);dnDSA^+组排斥反应发生率为62.5%,显著高于HLA^-组的8.57%和dnDSA^-组的8.69%,差异有统计学意义(P=0.013)。病理检查结果显示,dnDSA^+组受者移植肾中常伴发微循环炎症反应(肾小球炎和毛细血管炎)及损伤(毛细血管基底膜多层样变)和C4d阳性染色,但瘢痕程度、动脉纤维化和小管间质性炎症均与dnDSA无明显相关。结论dnDSA阳性率与HLA错配位点数有关,dnDSA的出现会降低移植物长期存活率,增加排斥反应发生率,dnDSA所致的排斥反应常伴有微循环炎症反应和C4d染色阳性。

Objective To explore the relationship between positive rate of de novo donor specific antibody (dnDSA) and human leukocyte antigen (HLA) mismatch after kidney transplantation and explore the impact of dnDSA upon long-term graft survival and rejection. Methods Retrospective analysis was conducted for clinical data of 101 kidney transplant recipients. Based upon HLA antibody and dnDSA, they were divided into three groups of HLA^-(n=70), dnDSA-(n=23) and dnDSA+(n=8). Rejection and graft survival were recorded for evaluating the impact of dnDSA on rejection and graft survival and observing the differences among all groups. Results The mismatchs of HLA-A/B and HLA-DR were more frequent than HLA^- and dnDSA^- groups(P=0.047, P=0.010)and graft survival was lower in dnDSA^+ group than HLA^- and dnDSA^- groups (P=0.001). The rejection rate was higher in dnDSA^+ group (62.5%) than HLA^- group (8.57%) and dnDSA^- group (8.69%). The difference was statistically significant (P=0.013). Pathological examination indicated microcirculatory inflammation (glomerulonephritis & trichodangiitis) and damage (multilayer change of capillary basement membrane) occurred frequently in dnDSA^+ group and C4d remained positive. However, scar, arterial fibrosis or tubulointerstitial inflammation was not correlated with dnDSA. Conclusions HLA mismatch is correlated with dnDSA positivity. And dnDSA may reduce graft survival and enhance rejection rate. Rejection mediated by dnDSA is often accompanied by microcirculatory inflammation and C4d positivity.