HLA相合供受者杀伤细胞免疫球蛋白样受体基因分布规律及其在异基因造血干细胞移植中的作用

Distribution of KIR gene in HLA-identical donor and recipient and its role in allogeneic hematopoietic stem cell transplantation

目的探讨HLA相合的供受者间KIR基因分布特征以及供者KIR-受者HLA模式对异基因造血干细胞移植预后的影响。方法采用PCR-SSOP的方法检测了80对供受者样本的KIR基因,回顾性分析了其中56例患者异基因造血干细胞移植预后情况,包括中性粒细胞和血小板重建时间、a GVHD发生情况以及总生存时间,探讨供者KIR-受者HLA配体模式对异基因造血干细胞移植预后的影响。结果在所有80对供受者样本中,共检测出16个KIR基因和22种KIR基因型,其中KIR2DL1、KIR2DP1、KIR2DL3和KIR3DL1基因表现为高频,KIR2DS3基因出现频率最低,供受者中分布频率最高的基因型是AA1,其次是Bx2,KIR基因和基因型在供受者间分布无明显差异。56例患者按照供者KIR-受者HLA配体模式进行分组比较发现,对于KIR2DL1、KIR2DL3全阳性的供者,无论配基HLA-C相合还是错配,对中性粒细胞和血小板重建时间、a GVHD的分级和总生存时间均无影响;而对于KIR3DL1阳性的供者,在配基完全相合的状态下即受者配基为HLA-Bw4纯合子时,中性粒细胞重建时间长,而在血小板重建时间、a GVHD的分级和总生存时间影响不大。结论在异基因造血干细胞移植前检测供者的KIR基因分型,对改善移植后免疫重建状态有一定意义。

Objective To investigate the distribution characteristics of KIR gene between HLA-identical donors and recipients and the effect of donor KIR-recipient HLA pattern on the prognosis of allogeneic hematopoietic stem cell transplantation.Methods The KIR gene of 80 pairs of donors and recipients was detected by PCR-SSOP method. The 56 patients were retrospectively analyzed after allogeneic hematopoietic stem cell transplantation,including reconstitution time for neutrophil and platelet,a GVHD and overall survival,exploring the impact of donor’s KIR-recipient’s HLA pattern on the prognosis of allogeneic hematopoietic stem cell transplantation. Results A total of 16 KIR genes and 22 KIR genotypes were detected in all the 80 pairs of donors and recipients. The KIR2 DL1,KIR2 DP1,KIR2 DL3 and KIR3 DL1 genes showed high frequency,and the KIR2 DS3 gene had the lowest frequency between donors and recipients. The most frequent genotype was AA1,followed by Bx2,and there was no statistical significance on the difference for the distribution of KIR gene and genotype between donors and recipients. Fifty-six patients were compared among the three groups according to donor’s KIR-recipient’s HLA pattern. For donors with KIR2 DL1 and KIR2 DL3 positive,there was no effect on reconstitution time of neutrophil and platelet,the grade of a GVHD and overall survival time,regardless of HLA-C ligands are identical or mismatch. For KIR3 DL1-positive donors,the reconstitution time of neutrophil was longer when the ligands were homozygous for HLA-Bw4. There was little effect on platelet reconstitution time,grade of a GVHD,and overall survival. Conclusion The detection of KIR genotyping in donors before allogeneic hematopoietic stem cell transplantation has a certain significance on improving the status of post-transplant immune reconstitution.