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目的 探讨不同激活性杀伤细胞免疫球蛋白样受体(KIR)在人类白细胞抗原(HLA)全相合无关供体异基因造血干细胞移植中的作用。方法 采用序列特异性引物聚合酶链反应(PCR-SSP)和基因测序(SBT)方法,对中国造血干细胞捐献者资料库中提供的74对HLA全相合供受者进行KIR及HLA高分辨分型,其中38例进行异基因造血干细胞移植,接受移植的患者FAB分型为急性淋巴细胞白血病(ALL)18例、慢性粒细胞白血病(CML8)例、急性髓系白血病(AML)12例,移植后的患者随访到2008年12月。结果 在74对供受者中100.00﹪有KIR2DS4基因,64.87﹪有KIR2DS1基因,60.81﹪有KIR3DS1基因,45.95﹪有KIR2DS5基因,44.60﹪有KIR2DS2基因,35.14﹪有KIR2DS3基因。在AML和CML分型的移植中供者有激活性KIR2DS1、KIR2DS3和KIR3DS1基因高表达;而在ALL分型的移植中低表达。在表达KIR2DS4的供受者中,其中51.40﹪仅表达2DS4*001/002亚型,23.60﹪仅表达2DS4*003-007亚型,25.00﹪为两种亚型同时表达。供受者仅有2DS4*001/002亚型的病例均在移植后死亡;供者具有2DS4*003-007亚型的病例1年无病生存率为83.30﹪。当供者aKIR基因数目≥3个时,ALL患者的1年无病生存率为87.50﹪;当供者aKIR基因数目<3个时,AML/CML患者1年无病生存率为83.33﹪。结论 在无关供体异基因造血干细胞移植中,KIR单体型A、激活性KIR受体基因亚型和数目的差异表达,对降低GVHD的发生和移植的预后起关键作用。
Objective To investigate the role of different killer cell immunoglobulin-like receptors (KIRs) in human leukocyte antigen (HLA) non-donor allograft donor allogeneic hematopoietic stem cell transplantation. Methods 74 pairs of HLA-matched donors provided by China hematopoietic stem cell donor database were subjected to KIR and HLA high resolution typing by PCR-SSP and SBT. , Of which 38 cases were allogeneic hematopoietic stem cell transplantation. The patients undergoing FAB classification were 18 cases of acute lymphoblastic leukemia (ALL), 12 cases of chronic myeloid leukemia (CML8) and 12 cases of acute myeloid leukemia (AML) after transplantation Of patients were followed up until December 2008. Results There were KIR2DS4 gene in 100.00% of 74 donors, KIR2DS1 gene in 64.87%, KIR3DS1 gene in 60.81%, KIR2DS5 gene in 45.95%, KIR2DS2 gene in 44.60% and KIR2DS3 gene in 35.14%. Donor-positive KIR2DS1, KIR2DS3 and KIR3DS1 genes were highly expressed in AML and CML-typed grafts but were low in ALL-typed grafts. Among the recipients expressing KIR2DS4, 51.40% expressed only 2DS4 * 001/002 subtypes, 23.60% expressed only 2DS4 * 003-007 subtypes, and 25.00% expressed both subtypes simultaneously. Only recipients with 2DS4 * 001/002 subtypes died after transplantation. The 1 year disease-free survival rate of patients with 2DS4 * 003-007 subtypes was 83.30%. When the number of donor aKIR genes was ≥3, the one-year disease-free survival rate of ALL patients was 87.50%. When the number of donor aKIR genes was less than 3, the one-year disease-free survival rate of AML / CML patients was 83.33%. Conclusions The differential expression of KIR haplotype A and KIR receptor subtypes and their numbers in unrelated donor allogeneic hematopoietic stem cell transplantation play a key role in reducing the incidence of GVHD and the prognosis of transplantation.