Reinsmoen N L, Matas A J
Department of Surgery, University of Minnesota, Minneapolis 55455.
Transplantation. 1993 May;55(5):1017-23. doi: 10.1097/00007890-199305000-00013.
Previous studies suggest stable renal transplant recipients can have either prednisone (P) or cyclosporine withdrawn; however, 30% of these patients undergo rejection requiring reinstitution of P or CsA. Some patients return to baseline creatinine levels, while others either stabilize at a higher creatinine level or lose their graft. It would be ideal to establish immunologically based criteria for selecting patients who can be successfully withdrawn or tapered from immunosuppression. We have investigated the development of donor antigen-specific hyporeactivity by using donor cells and/or homozygous typing cells defining the HLA-Dw specificities of the donor cells as stimulator cells in the mixed lymphocyte culture (MLC) and comparing the pre- and posttransplant responses of peripheral blood mononuclear cells from 199 kidney transplant recipients. Of these, 27% of the haploidentical living-related donor and 25% of the cadaver recipients developed in vitro donor antigen-specific hyporeactivity. The LRD recipients who did so have lower mean creatinine levels at 6, 12, and 24 months posttransplant (1.3, 1.3, and 1.2, respectively) than those who remained responsive to the donor antigens (1.6, 1.7, and 1.8) (P < 0.05). However, no differences in the mean creatinine levels were observed between CAD recipients who developed donor antigen-specific hyporeactivity and those who remained responsive. Rejection episodes were common in all groups in the first 3 months posttransplant; however, recipients who developed donor antigen-specific hyporeactivity tended to experience fewer rejection episodes after 3 months posttransplant. The percentage of recipients who remained rejection-free after 3 months post-transplant was 95% for CAD recipients who developed donor antigen-specific hyporeactivity vs. 83% for those who remained responsive. Only 1 hyporesponsive recipient (0/15 LRD; 1/20 CAD) developed chronic rejection vs. 12 (5/41, LRD; 7/60, CAD) recipients who remained responsive. For those with graft function at 3 months (when hyporesponsiveness was first determined), the actuarial 36-month graft survival was higher in the hyporesponsive (92%, LRD; 94%, CAD) than in responsive groups (LRD, 76%; CAD, 91%). No differences in the degree of HLA-DR mismatching (MM) were observed for the LRD hyporesponsive (1.20 DR MM) vs. reactive (0.98 DR MM) groups or for the CAD hyporesponsive (1.35 DR MM) vs. reactive (1.30 DR MM) groups. Donor antigen-specific hyporeactivity could not be determined (UND) for 30 of the LRD recipients and 33 of the CAD recipients due to lack of mismatching for DR antigens (0.03 DR MM and 0.25 DR MM, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
以往研究表明，稳定的肾移植受者可以停用泼尼松（P）或环孢素；然而，这些患者中有30%会发生排斥反应，需要重新使用P或环孢素A（CsA）。一些患者的肌酐水平恢复到基线，而另一些患者要么稳定在较高的肌酐水平，要么失去移植肾。建立基于免疫学的标准来选择能够成功停用或减少免疫抑制的患者将是理想的。我们通过使用供体细胞和/或定义供体细胞HLA-Dw特异性的纯合分型细胞作为混合淋巴细胞培养（MLC）中的刺激细胞，并比较199例肾移植受者外周血单个核细胞移植前后的反应，来研究供体抗原特异性低反应性的发展情况。其中，27%的单倍体亲属活体供者和25%的尸体供者受者出现了体外供体抗原特异性低反应性。出现低反应性的亲属活体供者受者在移植后6个月、12个月和24个月时的平均肌酐水平（分别为1.3、1.3和1.2）低于对供体抗原仍有反应的受者（分别为1.6、1.7和1.8）（P<0.05）。然而，在出现供体抗原特异性低反应性的尸体供者受者和仍有反应的受者之间，未观察到平均肌酐水平的差异。移植后前3个月所有组排斥反应均常见；然而，出现供体抗原特异性低反应性的受者在移植后3个月后排斥反应往往较少。移植后3个月仍无排斥反应的受者百分比，出现供体抗原特异性低反应性的尸体供者受者为95%，仍有反应的受者为83%。只有1例低反应性受者（0/15例亲属活体供者；1/20例尸体供者）发生慢性排斥反应，而仍有反应的受者有12例（亲属活体供者5/41例；尸体供者7/60例）。对于移植后3个月时具有移植肾功能（此时首次确定低反应性）的患者，低反应性组（亲属活体供者92%；尸体供者94%）移植肾36个月的预期生存率高于有反应组（亲属活体供者76%；尸体供者中91%）。对于亲属活体供者低反应性组（1.20个DR错配）与有反应组（0.98个DR错配）或尸体供者低反应性组（1.35个DR错配）与有反应组（1.30个DR错配），未观察到HLA-DR错配程度的差异。由于DR抗原缺乏错配（分别为0.03个DR错配和0.25个DR错配），30例亲属活体供者受者和33例尸体供者受者无法确定供体抗原特异性低反应性（UND）。（摘要截断于400字）
