2月20日，我所吴德沛教授课题组与江苏省血液研究所何军研究员课题组在《Biologyof Blood and Marrow Transplantation》上发表题为“KIR2DS4 and ItsVariant KIR1D Are Associated with Acute Graft-versus-Host Disease, Cytomegalovirus,and Overall Survival after Sibling-Related HLA-Matched Transplantation inPatients with Donors with KIR Gene Haplotype A”的研究论文，吴德沛教授和何军研究员为该文的共同通讯作者。
NK细胞的功能是通过杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-like receptor，KIR)来调节的。KIR通过与靶细胞表面相应的MHC-I类分子结合，传导激活或抑制信号，从而调控NK细胞的激活或者抑制。之前我们研究组报道KIRAA单体型是汉族人群中最重要的单体型，占一半以上。2DS4是KIRAA单体型唯一的激活性受体，而KIR1D是2DS4的变异体，变异体存在框架移位，导致蛋白不完整，不能锚定在细胞膜上，最终导致无法传递激活性信号。对于KIRDS4基因在造血干细胞移植中是否起到一定作用，目前尚未见大样本的报道。
我们随访了HLA全相合的同胞供受体267对，对供受体的KIR基因分型进行检测，将供体单体型为AA型的患者，根据供体的KIR2DS4/KIR1D分布，分为2DS4+2DS4+、2DS4+1D+和1D+1D+三组，研究三组患者在植入，aGVHD，CMV感染，复发，TRM和OS的差异。我们结果提示在受试者中KIR2DS4基因及变异体KIR1D呈偏态分布。对于供体为KIRAA单体型，行同胞全相合allo-HSCT的患者，KIR2DS4基因分型对移植预后存在影响， 1D+1D+组患者重度GVHD和CMV感染发生率高，无病生存下降，1D+1D+组供体尽可能避免选择。
原文摘要：Outcomes forhematopoietic stem cell transplantation (HSCT) in various donor and recipientkiller immunoglobulin-like receptor (KIR) genotypes have been studiedextensively. The associations between KIR2DS4 and its variant KIR1D withoutcomes of HSCT from a sibling-related HLA-matched donor with KIR haplotype Ahave not been explored, however. To study this, we genotyped donor-recipientpairs and divided 165 recipients of HSCT from a KIR gene haplotype A donor into3 groups: 2DS4+/2DS4+ (2 intact KIR2DS4 alleles), 2DS4+/1D+ (heterozygous), and1D+/1D+ (homozygous for the deletion variant KIR1D). No difference in therecovery of neutrophils and platelets among the 3 groups was observed. Thecumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD)within day +100 was 28.94% in the 2DS4+/2DS4+ group, 14.11% in the 2DS4+/1D+group, and 44.44% in the 1D+/1D+ group (P = .0159). Multivariate analysisidentified 1D+/1D+ as an independent risk factor for aGVHD (hazard ratio [HR],4.221; 95% confidence interval [CI], 1.470 to 12.124; P = .007). In contrast,the cumulative incidences of chronic GVHD, 3-year cumulative relapse, andtreatment-related mortality did not differ significantly among the 3 groups.The rate of cytomegalovirus (CMV) reactivation was 46.96% in the 2DS4+/2DS4+group, 20.16% in the 2DS4+/1D+ group, and 53.25% in the 1D+/1D+ group (P =.0017). Multivariate analysis identified 2DS4+/1D+ as an independent protectivefactor for CMV reactivation (HR, 0.268; 95% CI, 0.125 to 0.574; P = .001).Although overall survival (OS) did not differ among the groups in the firstyear, the 2DS4(+)/2DS4(+) group had significantly better OS than the othergroups after 1 year (P = .0361). In patients with advanced-stage disease, the3-year probability of disease-free survival was 51.06% in the 2DS4+/2DS4+group, 34.01% in the 2DS4+/1D+ group, and 0% in the 1D+/1D+ group (P = .0314).Collectively, our data suggest that the KIR 2DS4/1D allelic variance isassociated with the outcome of sibling-related HLA-matched HSCT, and that donorsubclassification of KIR 2DS4/1D alleles should be considered in this setting.
原文链接：http://dx.doi.org/10.1016/j.bbmt.2015.10.004
