抑制性和激活性免疫球蛋白样受体在亲缘半相合造血干细胞移植中的作用

目的 分别探讨NK细胞中抑制性和激活性免疫球蛋白样受体(KIR)在亲缘半相合造血干细胞移植(HSCT)中的作用.方法 检测47例亲缘半相合HSCT中的供者KIR基因型和患者HLA-C基因型,随访移植后2年总生存率、Ⅲ～Ⅳ度急性移植物抗宿主病(GVHD)发生率和复发率.结果 ①按供受者抑制性KIR与其配体HLA-C是否匹配分为两组,匹配组的2年总生存率明显高于不匹配组[分别为(87.5±8.3)%和(54.5±9.0)%,P=0.03];复发率明显降低[分别为0和(25.4±9.5)%,P=0.05].将病例分为髓系白血病和淋巴细胞白血病,其中30例髓系白血病患者中匹配组复发率明显低于不匹配组[分别为0和(35.0±14.4)%,P=0.04].其他项目差异无统计学意义.②常见的激活性KIR主要包括3个:KIR2DS1、KIR2DS2、KIR2DS3.分别按其供者是否表达进行单因素分析,其中KIR2DS1(+)组Ⅲ～Ⅳ度急性GVHD发生率比KITR2DS1(-)组低(分别为13%和28%,P＞0.05);KIR2DS2(+)组复发率低于KIR2DS2(-)组[分别为0和(17.3±7.1)%,P＞0.05];KIR2DS3(+)组Ⅲ～Ⅳ度急性GVHD发生率低于KIR2DS3(-)组(分别为11%和26%,P＞0.05);其他无明显差异.结论 ①亲缘半相合HSCT中,供者抑制性KIR与患者HLA-C匹配组较不匹配组总体生存率明显升高,复发率明显降低.特别在髓系白血病中,复发率明显降低.②对于激活性KIR受体中KIR2DS1或KIR2DS3的表达,可能降低急性重度GVHD的发生率;而KIR2DS2(+)组表达,可能降低复发率.

Abstract：

Objective To investigate the effect of inhibitory and activating KIRs on a cohort of Chinese leukemia patients who received haplo-identical hematopoietic stem cell transplantation (HSCT).Methods Donor' s inhibitory and activating KIRs and recipient' s HLA-C from 47 cases who received haplo-identical HSCT were tested by PCR-SSP.2 year overall survival ( OS), incidence of severe ( grade Ⅲ to Ⅳ )acute GVHD (aGVHD) and relapse rate(RR) were analyzed.Results ①According to Matched (M) vs Mis-Matched( MM ) between donor' s inhibitory KIR and recipient' s HLA-C1/C2 subgroup, 2 year OS rate in M group[(87.5 ±8.3)%]was significantly higher than that in MM group (54.5 ±9.0)%, (P=0.03).Lower incidence of relapse rate was seen in M group than in M/MM groups[0 vs (25.4 ±9.5)%, P =0.05].In 30 cases of myeloid leukemia patients, there was lower RR in M group than in MM groups[0 vs (35.0 ± 14.4) % ,P = 0.04].②According to the 3 activating KIR genes: KIR2DSI/KIR2DS2/KIR2DS3,lower incidence of grade Ⅲ - Ⅳ aGVHD was seen in KIR2DS1 ( + ) group than in KIR2DS1 ( - ) group ( 13% vs 28%, respectively, P＞0.05); and so was done in KIR2DS3( + ) group( 11% vs 26%, respectively, P＞0.05).The RR was lower in KIR2DS2( + ) group[0% vs (17.3 +7.1)%, respectively, P＞0.05].Conclusions In our haplo-identical HSCT setting, match between donor' s inhibitory KIR and recipient's HLA-C can significantly reduce the incidence of relapse rate and improve OS.Although lower incidences of severe aGVHD are noted in the donors with KIR2DS1 ( + ) or KIR2DS3 ( + ), and lower relapse rate is noted in the donors with KIR2DS2( + ) but without statistic difference, no remarkable effects of activating KIRs on OS have been found in our relatively small clinical series.

The effect of inhibitory and activating natural killer cell immunoglobulin receptor on haplo-identical hematopoietic stem cell transplantation

Objective To investigate the effect of inhibitory and activating KIRs on a cohort of Chinese leukemia patients who received haplo-identical hematopoietic stem cell transplantation (HSCT).Methods Donor' s inhibitory and activating KIRs and recipient' s HLA-C from 47 cases who received haplo-identical HSCT were tested by PCR-SSP.2 year overall survival ( OS), incidence of severe ( grade Ⅲ to Ⅳ )acute GVHD (aGVHD) and relapse rate(RR) were analyzed.Results ①According to Matched (M) vs Mis-Matched( MM ) between donor' s inhibitory KIR and recipient' s HLA-C1/C2 subgroup, 2 year OS rate in M group[(87.5 ±8.3)%]was significantly higher than that in MM group (54.5 ±9.0)%, (P=0.03).Lower incidence of relapse rate was seen in M group than in M/MM groups[0 vs (25.4 ±9.5)%, P =0.05].In 30 cases of myeloid leukemia patients, there was lower RR in M group than in MM groups[0 vs (35.0 ± 14.4) % ,P = 0.04].②According to the 3 activating KIR genes: KIR2DSI/KIR2DS2/KIR2DS3,lower incidence of grade Ⅲ - Ⅳ aGVHD was seen in KIR2DS1 ( + ) group than in KIR2DS1 ( - ) group ( 13% vs 28%, respectively, P＞0.05); and so was done in KIR2DS3( + ) group( 11% vs 26%, respectively, P＞0.05).The RR was lower in KIR2DS2( + ) group[0% vs (17.3 +7.1)%, respectively, P＞0.05].Conclusions In our haplo-identical HSCT setting, match between donor' s inhibitory KIR and recipient's HLA-C can significantly reduce the incidence of relapse rate and improve OS.Although lower incidences of severe aGVHD are noted in the donors with KIR2DS1 ( + ) or KIR2DS3 ( + ), and lower relapse rate is noted in the donors with KIR2DS2( + ) but without statistic difference, no remarkable effects of activating KIRs on OS have been found in our relatively small clinical series.