Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Hematology and Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Pediatr Transplant. 2020 Sep;24(6):e13728. doi: 10.1111/petr.13728. Epub 2020 Jun 27.
Killer Ig-like receptor 2DS4 (KIR2DS4) is the most prevalent activating killer Ig-like receptor gene. It is divergent and encodes either full-length or deleted allele variants. The studies of donor killer KIR2DS4 in unrelated allogeneic hematopoietic stem cell transplantations were limited.
KIR and HLA genotyping were determined in 75 pairs of Chinese pediatric hematologic malignancy patients.
Among the 75 donor-recipient pairs, 77.3% (58/75) of the donors were positive for full-length KIR2DS4 and 22.7% (17/75) were negative. Patients who had donors positive for full-length KIR2DS4 had higher cumulative incidence of aGVHD than patients whose donor negative for full-length KIR2DS4 (86.2% versus 76.5%, P = .038). Multivariate analysis showed full-length KIR2DS4 was the significant factor for I-IV aGVHD (HR = 2.166, 95% CI: 1.01-4.26, P = .025). Subgroup analysis showed that AML and CML patients who received donors negative for full-length KIR2DS4 have a higher cumulative incidences of cGVHD (75% vs 62%, P = .008). There were no significant effects of full-length KIR2DS4 on overall survival (P = .13), relapse-free survival (P = .14), CMV reactivation (P = .52), and relapse (HR = 0.38, 95% CI: 0.09-1.6, P = .1875).
Our findings indicated a significant correlation of donor full-length KIR2DS4 on aGVHD and cGVHD. These results suggested that combining KIR and HLA genotyping may help make a better sense of transplants in these patients.
杀伤细胞免疫球蛋白样受体 2DS4（KIR2DS4）是最常见的激活杀伤细胞免疫球蛋白样受体基因。它具有变异性，可编码全长或缺失等位基因变异体。在无关异基因造血干细胞移植中，对供体杀伤 KIR2DS4 的研究有限。
对 75 对中国儿科血液恶性肿瘤患者的 KIR 和 HLA 基因进行分型。
在 75 对供受者中，77.3%（58/75）的供者为全长 KIR2DS4 阳性，22.7%（17/75）为阴性。与全长 KIR2DS4 阴性的供者相比，全长 KIR2DS4 阳性的患者发生急性移植物抗宿主病的累积发生率更高（86.2%比 76.5%，P=0.038）。多变量分析显示，全长 KIR2DS4 是 I-IV 级急性移植物抗宿主病的显著因素（HR=2.166，95%CI：1.01-4.26，P=0.025）。亚组分析显示，接受全长 KIR2DS4 阴性供者的 AML 和 CML 患者发生慢性移植物抗宿主病的累积发生率更高（75%比 62%，P=0.008）。全长 KIR2DS4 对总生存（P=0.13）、无复发生存（P=0.14）、CMV 再激活（P=0.52）和复发（HR=0.38，95%CI：0.09-1.6，P=0.1875）均无显著影响。
本研究结果表明，供体全长 KIR2DS4 与急性移植物抗宿主病和慢性移植物抗宿主病显著相关。这些结果表明，结合 KIR 和 HLA 基因分型可能有助于更好地理解这些患者的移植情况。
