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目的探讨杀伤细胞免疫球蛋白样受体/人类白细胞抗原(KIR/HLA)受配体模式及移植后抑制性杀伤免疫球蛋白类受体(iKIR)的表达对单倍体造血干细胞移植预后的影响。方法采用序列特异性引物聚合酶链反应(SSP-PCR)方法,对14对HLA半相合供/受者移植前进行KIR与HLA分型,同时分析KIR/HLA的受配体模式,用四色流式细胞技术对其中8例患者在移植后检测CD158a(KIR2DL1)、CD158b(KIR2DL2)、CD158e(KIR3DL1)的表达。结果 3例受者表达供者所有iKIR相应配体HLA-C2、C1、Bw4,此3对供受者即为KIR配体相合组;另外11对存在KIR配体缺失的供受者则为KIR配体迷失组。KIR配体迷失组患者移植后中性粒细胞及血小板重建时间较KIR配体相合组均较晚,但差异无统计学意义(P>0.05)。KIR配体迷失组患者移植后2年持续缓解率和2年总生存率高于KIR配体相合组,但差异无统计学意义(P>0.05)。移植后监测iKIR发现受者均表达供者型iKIR,4例患者复发时监测NK细胞及iKIR表达明显降低。结论在HLA半相合造血干细胞移植中,移植后动态监测iKIR的表达可预示复发,KIR/HLA受配体错配可能有助于提高移植后缓解率和总生存率。
Objective To investigate the effect of killer cell immunoglobulin-like receptor / human leukocyte antigen (KIR / HLA) ligand pattern and the expression of iKIR on the prognosis of haploid hematopoietic stem cell transplantation . Methods KIR and HLA typing were performed on 14 pairs of HLA haploidentical donor / recipient prior to transplantation using sequence-specific primer-polymerase chain reaction (SSP-PCR). KIR / HLA ligand patterns were also analyzed. Four- Flow cytometry was used to detect the expression of CD158a (KIR2DL1), CD158b (KIR2DL2) and CD158e (KIR3DL1) in 8 of 8 patients after transplantation. Results Three recipients expressed HLA-C2, C1 and Bw4 ligands of all iKIR donors, and the three pairs of donors were KIR ligand matched groups. Another 11 donors with KIR ligand deletion were KIR Lost group of ligands. Neutrophil and platelet reconstruction time were longer in patients with KIR Ligand than in KIR Ligand, but the difference was not statistically significant (P> 0.05). The sustained remission rate and 2-year overall survival rate at 2 years after transplantation in KIR ligand lost group was higher than that in KIR ligand matched group, but the difference was not statistically significant (P> 0.05). After transplantation, iKIR was detected in all recipients, and iKIR was detected in 4 recipients. The expression of iKIR and NK cells were significantly decreased in 4 patients. Conclusions In HLA haploidentical hematopoietic stem cell transplantation, the dynamic monitoring of iKIR expression after transplantation may indicate recurrence. Mismatch of KIR / HLA ligand may be helpful to improve the post-transplantation remission rate and overall survival rate.