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肝移植后,通过 adoptive immunotherapy 可克服 fc-γ 受体多态性导致的血流感染遗传易感性。

Adoptive immunotherapy overcomes genetic susceptibility to bloodstream infections due to fc-gamma receptor polymorphisms after liver transplantation.

机构信息

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.

出版信息

Am J Transplant. 2022 Oct;22(10):2392-2400. doi: 10.1111/ajt.17113. Epub 2022 Jun 17.

Abstract

Single nucleotide polymorphisms (SNPs) in FCGR3A can predict the susceptibility of liver transplant (LT) recipients to bloodstream infections (BSI) and clinical outcomes following living-donor LT (LDLT). Here, we retrospectively analyzed the relationship of adoptive immunotherapy with activated natural killer (NK) cells from perfusate effluents of liver allografts against BSI following LDLT. Higher BSI incidence and lower survival were observed in LT recipients with FcγRIIIa (158F/F or F/V) (n = 81) who did not receive adoptive immunotherapy (n = 55) than in those who did (n = 26) (BSI frequency, 36.4% vs. 11.5%; p = .033; log-rank p = .047). After matching patient background using propensity score, similar results were obtained (BSI ratio, 41.7% vs. 12.5%; p = .049; log-rank p = .039). The predominant BSI pathogens in patients who did and did not receive adoptive immunotherapy were gram-negative rods (n = 3, 100%) and gram-positive cocci (GPC) (n = 15, 65.2%), respectively. The proportion of NK cells administered to patients with BSI was significantly lower than that administered to patients without BSI (Number: 80.3 (29.9-239.2) × 10 cells vs. 37.1 (35.6-50.4) × 10 ; p = .033, percentage; 14.1 (13.3-17.8)% vs. 34.6 (16.5-47)%, p = .0078). Therefore, adoptive immunotherapy with NK cells was associated with the reduced post-transplant BSI related to GPCs due to FcγRIIIa SNP in LT recipients.

摘要

FCGR3A 单核苷酸多态性 (SNP) 可预测肝移植 (LT) 受者发生血流感染 (BSI) 的易感性和活体供肝 LT (LDLT) 后的临床结局。在这里,我们回顾性分析了从肝移植供体灌流流出液中分离的活化自然杀伤 (NK) 细胞过继免疫治疗与 LDLT 后 BSI 的关系。在未接受过继免疫治疗(n=55)的 FcγRIIIa(158F/F 或 F/V)(n=81)的 LT 受者中,BSI 发生率较高,生存率较低(BSI 频率,36.4% vs. 11.5%;p=0.033;log-rank p=0.047),而接受过继免疫治疗(n=26)的患者则较低。通过倾向评分匹配患者背景后,也得到了类似的结果(BSI 比值,41.7% vs. 12.5%;p=0.049;log-rank p=0.039)。接受和未接受过继免疫治疗的患者的主要 BSI 病原体分别为革兰氏阴性杆菌(n=3,100%)和革兰氏阳性球菌(GPC)(n=15,65.2%)。发生 BSI 的患者给予的 NK 细胞数量明显低于未发生 BSI 的患者(数量:80.3(29.9-239.2)×10 细胞 vs. 37.1(35.6-50.4)×10 细胞;p=0.033,百分比;14.1(13.3-17.8)% vs. 34.6(16.5-47)%,p=0.0078)。因此,由于 LT 受者的 FcγRIIIa SNP,NK 细胞过继免疫治疗与 GPC 相关的移植后 BSI 减少有关。

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