Kröger Nicolaus, Binder Thomas, Zabelina Tatjana, Wolschke Christine, Schieder Heike, Renges Helmut, Ayuk Francis, Dahlke Joachim, Eiermann Thomas, Zander Axel
Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany.
Transplantation. 2006 Oct 27;82(8):1024-30. doi: 10.1097/01.tp.0000235859.24513.43.
The effect of natural killer (NK) cell alloreactivity on outcome of unrelated stem cell transplantation (SCT) remains controversial. Killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target cells, thereby regulating NK cell activity. The KIR genes are polymorphic and two broad haplotypes exist: KIR-haplotype A mainly encode for inhibitory receptors and only for one activating (KIR2DS4), whereas the group B haplotype encodes more for activating KIRs (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS5 und KIR3DS1).
The impact of KIR ligand mismatch on the number of activating and inhibitory donor KIR genes and on KIR-haplotype was studied on outcome of 142 patients with leukemia, who received standard myeloablative conditioning followed by in vivo T-cell depleted (ATG) unrelated SCT.
In a multivariate analysis KIR ligand mismatch had significantly higher treatment related mortality (RR 2.206, P = 0.03), resulting in reduced overall (RR 2.015, P = 0.02) and disease-free survival (RR 1.924, P = 0.03). In contrast, SCT from donors with group A haplotype (P = 0.003) or with low number of activating KIR genes (P = 0.005) resulted in reduced relapse rate with improved disease-fee survival (P = 0.04). This effect was seen only in acute myeloid leukemia/myelodysplastic syndrome and to a less extent in chronic myeloid leukemia. No effect was seen for acute lymphoblastic leukemia.
After in vivo T-cell depleted (ATG) unrelated stem cell transplantation with donors carrying low number of activating KIR genes (group A KIR haplotype), the risk of relapse is reduced and resulted in a significantly better disease-free survival.
自然杀伤（NK）细胞同种异体反应性对非亲缘干细胞移植（SCT）结局的影响仍存在争议。杀伤细胞免疫球蛋白样受体（KIRs）识别靶细胞上的人类白细胞抗原C和B表位，从而调节NK细胞活性。KIR基因具有多态性，存在两种主要单倍型：KIR单倍型A主要编码抑制性受体，仅编码一种激活型受体（KIR2DS4），而B组单倍型则更多地编码激活型KIRs（KIR2DS1、KIR2DS2、KIR2DS3、KIR2DS5和KIR3DS1）。
研究了142例白血病患者接受标准清髓预处理后行体内T细胞去除（抗胸腺细胞球蛋白）非亲缘SCT的结局，分析KIR配体错配对激活型和抑制型供体KIR基因数量以及KIR单倍型的影响。
多因素分析显示，KIR配体错配的治疗相关死亡率显著更高（风险比2.206，P = 0.03），导致总生存率（风险比2.015，P = 0.02）和无病生存率降低（风险比1.924，P = 0.03）。相反来自具有A组单倍型供体的SCT（P = 0.003）或激活型KIR基因数量少的供体（P = 0.005）导致复发率降低，无病生存率提高（P = 0.04）。这种效应仅在急性髓系白血病/骨髓增生异常综合征中可见，在慢性髓系白血病中程度较轻。急性淋巴细胞白血病未见此效应。
在接受体内T细胞去除（抗胸腺细胞球蛋白）的非亲缘干细胞移植后，供体激活型KIR基因数量少（A组KIR单倍型），复发风险降低，无病生存率显著提高。
