Chen C, Busson M, Rocha V, Appert M-L, Lepage V, Dulphy N, Haas P, Socié G, Toubert A, Charron D, Loiseau P
Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, CIB-HOG, AP-HP, Paris, France.
Bone Marrow Transplant. 2006 Sep;38(6):437-44. doi: 10.1038/sj.bmt.1705468. Epub 2006 Aug 7.
Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.
人类白细胞抗原（HLA）与杀伤细胞免疫球蛋白样受体（KIR）的组合可能会影响去T细胞造血干细胞移植（HSCT）的结果。KIR基因家族包括抑制性受体（KIR2DL和3DL）和激活性受体（KIR2DS）。抑制性KIR的配体是HLA - C（KIR2D）和HLA - Bw4（KIR3DL1），而激活性KIR的配体尚不清楚。供体和受体的激活性KIR基因型对HSCT结果的影响鲜有文献记载。在此，我们测定了131对非去T细胞的HLA全相合同胞HSCT供受者的HLA和KIR基因型。即使在髓系恶性肿瘤中，也未检测到“缺失KIR配体”对急性移植物抗宿主病（GVHD）、复发、生存率或感染有影响。然而，与受者基因型相比，供体中额外的激活性KIR基因，或供体与受者激活性KIR基因型相同，与较低的移植相关死亡率（TRM）相关（P = 0.005），在多变量分析中与更好的生存率相关（P = 0.02，风险比[HR]=0.28；P = 0.013，HR = 0.29），以及较低的巨细胞病毒（CMV）再激活发生率相关（P = 0.009，HR = 0.36）。这些数据突出了供体激活性KIR基因对HLA全相合同胞HSCT中TRM、总生存率和CMV再激活的影响。
