Rodriguez Daniel S, Jankowska-Gan Ewa, Haynes Lynn D, Leverson Glenn, Munoz Alejandro, Heisey Dennis, Sollinger Hans W, Burlingham William J
Department of Surgery, University of Wisconsin, Madison, WI, USA.
Am J Transplant. 2004 Apr;4(4):537-43. doi: 10.1111/j.1600-6143.2004.00385.x.
We hypothesized that donor/recipient sharing of the human leukocyte antigen (HLA) involved in allopeptide presentation to the T regulatory cell increases the incidence of immune regulation, thus contributing to long-term graft survival. Peripheral blood mononuclear cells (PBMC) were obtained from 40 living related donor (LRD) and 31 cadaver renal transplant recipients. The trans vivo delayed type hypersensitivity (DTH) assay was used to assign patients to regulator, nonregulator, and sensitized categories. In a large cohort (n=1934 patients), primary graft survival and rejection episodes were analyzed using a log rank test for comparison with the DTH results. The highest incidence of regulated anti-donor DTH was observed in the LRD HLA-identical group (6/6; 100%) followed by the LRD HLA 1 haplotype matched group (18/27; 67%). Within the cadaver population, two DR-matched recipients had a higher frequency of regulated anti-donor DTH (6/11; 55%) than 1 & 0 DR-matched recipients (3/18; 17%). In a multivariate model, matching for HLA-DR alone, or for DR plus DQ was significantly (p=0.045, p=0.041) correlated with DTH regulation. The better HLA-matched groups showed the highest incidence of DTH regulation and, in a larger retrospective analysis, displayed better graft survival and freedom from acute rejection (p<0.0001). HLA matching, and HLA-DR matching in particular, correlates with the incidence of immune regulation after kidney transplantation.
我们推测，供体/受体共享参与向调节性T细胞呈递同种异体肽的人类白细胞抗原（HLA）会增加免疫调节的发生率，从而有助于移植器官的长期存活。从40名活体亲属供体（LRD）和31名尸体肾移植受者中获取外周血单个核细胞（PBMC）。采用体内迟发型超敏反应（DTH）试验将患者分为调节者、非调节者和致敏者类别。在一个大型队列（n = 1934例患者）中，使用对数秩检验分析原发性移植器官存活情况和排斥反应发作情况，以与DTH结果进行比较。在LRD HLA全相同组中观察到调节性抗供体DTH的发生率最高（6/6；100%），其次是LRD HLA 1单倍型匹配组（18/27；67%）。在尸体供体人群中，两名DR匹配的受者调节性抗供体DTH的频率（6/11；55%）高于1个DR匹配和0个DR匹配的受者（3/18；17%）。在多变量模型中，仅匹配HLA-DR或匹配DR加DQ与DTH调节显著相关（p = 0.045，p = 0.041）。HLA匹配更好的组显示DTH调节的发生率最高，并且在一项更大规模的回顾性分析中，显示出更好的移植器官存活率和无急性排斥反应（p < 0.0001）。HLA匹配，尤其是HLA-DR匹配，与肾移植后免疫调节的发生率相关。
