Hematology Department, Institut Català d'Oncologia, Hospital Dr. Josep Trueta, IDIBGI, Girona, Spain.
Hematology Department, Institut Català d'Oncologia, Hospital Dr. Josep Trueta, IDIBGI, Girona, Spain.
Biol Blood Marrow Transplant. 2017 Dec;23(12):2042-2047. doi: 10.1016/j.bbmt.2017.08.003. Epub 2017 Aug 4.
Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P = .005; HR, 2.11, 95% CI, 1.06 to 4.18; P = .033; and HR, 1.50; 95% CI, 1.05 to 2.15; P = .025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor.
次要组织相容性抗原 (miHA) 错配与同种异体干细胞移植后的移植物抗宿主病 (GVHD) 有关，但由于不同组获得的结果缺乏一致性，这种关联仍存在争议。供体的 CTLA-4 基因型已被报道与急性 GVHD 的出现有关。我们在 1295 名接受 HLA 完全匹配的同胞供体异基因移植的患者的大队列中，探讨了供体 CTLA-4 基因型对与 HA-1、HA-8 或 H-Y miHA 错配相关的急性 GVHD 发生率的影响。如果供体和受者在 HA-1、HA-8 或 H-Y 上不匹配，则急性 GVHD 的发生率较高，但只有当供体具有 CTLA-4 rs231775 AA 基因型时（危险比 [HR]，2.18；95%置信区间 [CI]，1.27 至 3.75；P=0.005；HR，2.11，95%CI，1.06 至 4.18；P=0.033；HR，1.50；95%CI，1.05 至 2.15；P=0.025）。相比之下，当供体具有 CTLA-4 rs231775 AG 或 GG 基因型时，并未发现这种急性 GVHD 发生风险增加。我们得出结论，对特定 miHA 错配的免疫反应受供体 CTLA-4 基因型的调节。
