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目的探索供者抑制性杀伤细胞免疫球蛋白样受体(killer cell immunoglobulin-like re- ceptor,KIR)和受者HLA遗传背景与血缘关系全相合造血干细胞移植(HSCT)预后的关系。方法采用反向序列特异性寡核苷酸探针(RSSOP)和(或)序列特异性引物PCR(PCR-SSP)分型技术检测HLA 基因型,采用PCR-SSP技术检测供者KIR基因型。对59例接受血缘关系HLA-ABDR全相合、非去除 T细胞HSCT的恶性血液病患者病例资料进行回顾性分析。结果Ⅱ-Ⅳ级急性移植物抗宿主病 (aGVHD)发生率在KIR-HLA相容组患者为32％,非相容组患者为78％,两者差异有统计学意义(P= 0．026);Ⅱ-Ⅳ级aGVHD在Bw4相容组患者为24％,Bw4非相容组患者为61％,差异亦有统计学意义(P=0．018)。真菌感染发生率在Bw4相容组患者为14％,Bw4非相容组患者为44％,前者显著低于后者(P=0．028)。髓系疾病中,真菌感染发生率在Bw4相容组与Bw4非相容组患者分别为12％和 80％,前者明显低于后者(P=0．002);C2相容组患者总生存(Overall survival,OS)率显著高于C2非相容组患者(P=0．01)。结论供者KIR和受者HLA遗传背景与血缘HIA全相合HSCT预后与 aGVHD发生率、OS率和真菌感染发生率均有相关关系。供者KIR与受者HLA相容时,受者aGVHD 发生率下降。选择Bw4相容的供者有助于减轻患者aGVHD及真菌感染发生率,选择C2相容的供者有助于提高患者OS率。研究结果为遗传学指标指导下供者优化选择提供分子依据,为临床制定治疗方案提供参考。
Objective To explore the relationship between the donor killer cell immunoglobulin-like re- ceptor (KIR) and recipient HLA genetic background and the prognosis of all-matched hematopoietic stem cell transplantation (HSCT). Methods HLA genotypes were detected by reverse transcription sequence-specific oligonucleotide probes (RSSOPs) and / or sequence-specific primers PCR (PCR-SSP). KIR genotypes were detected by PCR-SSP. The data of 59 cases of hematologic malignancies receiving HLA-ABDR matched and non-cancerous HSCT were analyzed retrospectively. Results The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) was 32% in KIR-HLA-compatible group and 78% in non-compatible group, the difference was statistically significant (P = 0.026 ); Grade IV-IV aGVHD was 24% in the Bw4-compatible group and 61% in the Bw4-incompatible group, with a statistically significant difference (P = 0.018). The incidence of fungal infections was 14% in the Bw4-compatible group and 44% in the Bw4-incompatible group, the former being significantly lower than the latter (P = 0.028). Myeloid disease, the incidence of fungal infection in Bw4 compatible group and Bw4 incompatibility patients were 12% and 80%, the former was significantly lower than the latter (P = 0.002); C2-compatible patients with total survival (Overall survival, OS) was significantly higher than C2 non-compatible patients (P = 0.01). CONCLUSION: The prognosis of fully matched HCC with HLA-matched HLA genotypes and donor HLA-DRs is associated with the incidence of aGVHD, OS rate and the incidence of fungal infection. When donor KIR is compatible with recipient HLA, the incidence of aGVHD in recipients decreases. Choosing a Bw4-compatible donor will help reduce the incidence of aGVHD and fungal infections in patients, and choosing a C2-compatible donor will help improve OS. The results provide the molecular basis for the optimal selection of donor under the guidance of genetic indicators, and provide a reference for clinical treatment plan.