The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia
The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia
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DOI：
10.1182/blood-2003-02-0438
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发表时间：
2004-02-15
期刊：
影响因子：
20.3
通讯作者：
Briggs, DC
中科院分区：
文献类型：
--
作者：
Cook, MA;Milligan, DW;Briggs, DC
杀伤免疫球蛋白样受体（KIRs）调节自然杀伤细胞（NK）和部分T细胞的细胞活性。抑制性kir的主要配体是HILA-C，根据抑制性kir的特异性，HILA-C可细分为2组。激活kir的配体是未知的。造血干细胞移植（HSCT）后，受体组织可能不表达移植物中存在的KIR配体，供体KIR和受体HLA-C类型的结合可能影响结果。对来自HLA匹配的兄弟姐妹进行骨髓（n = 112）和淋巴（n = 108）疾病hsct的220对供体-受体进行HLA和KIR基因型测定。在针对髓细胞疾病进行的造血干细胞移植中，2组HLA-C （C2）纯合子患者的总生存率低于携带1组HLA-C （C1）等位基因的患者（P < 0.005）。此外，只有当供体另外携带激活KIR基因KIR2DS2时，才会出现这种效果（P = 0.045）。在淋巴系统疾病患者中未见效果。因此，在骨髓白血病的hla匹配的兄弟姐妹HSCT中，C2等位基因纯合的患者接受来自携带KIR基因KIR2DS2的供体的移植，生存率显著降低。
Killer immunoglobulin-like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HILA-C, which subdivides into 2 groups based on the specificity of inhibitory KIRs. The ligands for activatory KIRs are unknown. Following hematopoietic stem cell transplantation (HSCT), recipient tissues may not express a ligand for KIRs present within the graft, and the combination of donor KIR and recipient HLA-C types could influence outcome. HLA and KIR genotypes were determined in 220 donor-recipient pairs from HILA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myelold disease, overall survival was worse in patients homozygous for group 2 HLA-C (C2) than in patients who carried a group 1 HLA-C (C1) allele (P < .005). Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (P = .045). No effect was seen in patients with lymphoid disease. Thus, in HLA-matched sibling HSCT for myeloid leukemia, patients, homozygous for C2 alleles receiving a graft from a donor carrying the KIR gene KIR2DS2 have a significantly reduced chance of survival.