Duan Lian-Ning, Han Hong-Xing, Liu Jing, Yan Hong-Min, Zhu Ling, Xue Mei, Ding Li, Zhu Pei-Yu, Wang Heng-Xiang, Ji Shu-Quan
Department of Hematology, General Hospital of Air Force, Beijing 100036, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):809-15.
The purpose of study was to investigate the impact of killer immunoglobulin-like receptor (KIR) and its ligand on haploidentical bone marrow transplantation. 74 cases were analyzed for the distribution frequencies and characteristics of KIR and its ligand as well as the impact of KIR ligand for the haploidentical bone marrow transplantation in terms of the overall survival, disease-free survival (DFS), GVHD and relapse. The results showed that among the 19 KIR genotypes currently nominated KIR2DL1, KIR2DL4 and KIR3DL2-3 could be detected in all the cases. Other high frequency genotypes included KIR3DP1 (98.6%), KIR2DP1 (98.6%), KIR3DL1 (97.3%) and KIR2DL3 (97.3%). Inhibitory receptor genotypes were 1.37-fold of activating receptor genotypes. KIR2DL1, KIR3DL2, KIR3DL3 and KIR2DL4 were found in all haplotypes and at least one genotype of KIR2DL2 and/or KIR2DL3 existed in all haplotypes. Among the 14 genotypes found in the test, the HLA-Cw7 was the most popular (37.8%) and the group 2 (HLA-Cw1, 3, 7, 8, 13, 14) recognized by KIR2DL2/2DL3 counted for 43.2%. The incompatibility of KIR for 32 cases of haploidentical BMT was 43.8%, of which 9/14 were KIR2DL incompatible, 5/14 were KIR2DL2 or KIR3DL1 incompatible. Among the 46 cases of haploidentical BMT, 29 cases were HLA-Cw matched and 14 cases were mismatched. The completed mismatch ratio of HLA-Cw was 30.4% and the match ratio was 63.4%. The survival rate was higher for the 14 cases of KIR genotype compatible group than the 13 cases of KIR genotype incompatible group (p = 0.032). The disease-free survival was significantly higher for the 17 cases of mismatched KIR ligands (HLA-Cw) group than the matched group (p = 0.024). The survival rate was higher in GVHD group than that in non-GVHD group when the KIR ligand was missing. The acute and severe GVHD was related to the existence of activating receptor of KIR2DS1/2DS2. The incompatibility group was accompanied with frequent acute and severe GVHD and less relapse and vice versa for the compatibility group. One patient died after BMT among the 14 mismatched KIR ligand group suffering from myelogenous leukemia while 4 patients out of 12 patients died in the matched group. It is concluded that the haploidentical BMT is characterized by mismatch between donor and recipient and its immunological reactions also features by the incompatibility of KIR genotype and missing ligand. The missing ligand for the donor KIR has strong effect on the outcome of BMT and it means a lot to analyze the KIR genotype and its ligand for the selection of best donor and prognostic evaluation in haploidentical BMT.
本研究旨在探讨杀伤细胞免疫球蛋白样受体（KIR）及其配体对单倍体相合骨髓移植的影响。分析74例患者KIR及其配体的分布频率、特征，以及KIR配体对单倍体相合骨髓移植的总生存、无病生存（DFS）、移植物抗宿主病（GVHD）和复发的影响。结果显示，在目前已命名的19种KIR基因型中，KIR2DL1、KIR2DL4和KIR3DL2 - 3在所有病例中均可检测到。其他高频基因型包括KIR3DP1（98.6%）、KIR2DP1（98.6%）、KIR3DL1（97.3%）和KIR2DL3（97.3%）。抑制性受体基因型是激活性受体基因型的1.37倍。所有单倍型中均存在KIR2DL1、KIR3DL2、KIR3DL3和KIR2DL4，且所有单倍型中至少存在一种KIR2DL2和/或KIR2DL3基因型。在检测到的14种基因型中，HLA - Cw7最为常见（37.8%），KIR2DL2/2DL3识别的第2组（HLA - Cw1、3、7、8、13、14）占43.2%。32例单倍体相合骨髓移植患者中KIR不相合率为43.8%，其中9/14为KIR2DL不相合，5/14为KIR2DL2或KIR3DL1不相合。46例单倍体相合骨髓移植患者中，29例HLA - Cw匹配，14例不匹配。HLA - Cw的完全不匹配率为30.4%，匹配率为63.4%。KIR基因型相合组的14例患者生存率高于KIR基因型不相合组的13例患者（p = 0.032）。KIR配体（HLA - Cw）不匹配组的17例患者无病生存率显著高于匹配组（p = 0.024）。KIR配体缺失时，GVHD组的生存率高于非GVHD组。急性和重度GVHD与KIR2DS1/2DS2激活性受体的存在有关。不相合组常伴有急性和重度GVHD且复发较少，相合组则相反。14例KIR配体不匹配的骨髓增生异常综合征患者中有1例在骨髓移植后死亡，而12例匹配组患者中有4例死亡。结论：单倍体相合骨髓移植的特点是供受者之间不匹配，其免疫反应也表现为KIR基因型不相合和配体缺失。供者KIR的配体缺失对骨髓移植结果有很大影响，分析KIR基因型及其配体对单倍体相合骨髓移植中最佳供者的选择和预后评估具有重要意义。
