Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Pediatr Transplant. 2023 May;27(3):e14475. doi: 10.1111/petr.14475. Epub 2023 Jan 23.
Late acute cellular rejection (ACR) is associated with donor-specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T-cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR. To test the hypothesis that the inflammatory milieu is associated with delayed response (DR) to rejection therapy, we performed a single-center retrospective case-control study of pediatric late liver ACR using multiparameter immunofluorescence for CD4, CD8, CD68, CD20, and CD138 to identify immune cell subpopulations.
Pediatric liver transplant recipients transplanted at <17 years of age and treated for biopsy-proven late ACR between January 2014 and 2019 were stratified into rapid response (RR) and DR based on alanine aminotransferase (ALT) normalization within 30 days of diagnosis. All patients received IV methylprednisolone as an initial rejection treatment. Immunofluorescence was performed on archived formalin-fixed paraffin embedded (FFPE) liver biopsy tissue.
Liver biopsies from 60 episodes of late ACR in 54 patients were included in the analysis, of which 33 were DR (55%). Anti-thymocyte globulin was only required in the DR group. The frequency of liver-infiltrating CD20 and CD8 lymphocytes and the prevalence of autoantibodies were higher in the DR group. In univariate logistic regression analysis, serum gamma-glutamyl transpeptidase (GGT) level at diagnosis, but not ALT, Banff score or presence of DSA, predicted DR.
Higher serum GGT level, presence of autoantibodies, and increased CD8 T-cell infiltration portends DR in late ACR treatment in children.
晚期急性细胞排斥（ACR）与供体特异性抗体（DSA）的发展、慢性排斥和移植物丢失有关。然而，缺乏晚期 ACR 治疗反应的准确预测指标。ACR 主要是 T 细胞介导的，但 B 细胞和浆细胞（PC）在晚期 ACR 期间也浸润门脉区。为了验证炎症环境与排斥治疗的延迟反应（DR）相关的假设，我们使用多参数免疫荧光法对 CD4、CD8、CD68、CD20 和 CD138 进行了一项单中心回顾性病例对照研究，以鉴定免疫细胞亚群，研究了儿科晚期肝脏 ACR。
2014 年 1 月至 2019 年间，<17 岁接受肝移植且因活检证实晚期 ACR 而接受治疗的儿科肝移植受者，根据诊断后 30 天内丙氨酸氨基转移酶（ALT）正常化情况，分为快速反应（RR）和 DR。所有患者均接受 IV 甲基强的松龙作为初始排斥治疗。对存档的福尔马林固定石蜡包埋（FFPE）肝活检组织进行免疫荧光分析。
纳入 54 例患者 60 例晚期 ACR 肝活检，其中 33 例（55%）为 DR。仅在 DR 组中需要使用抗胸腺细胞球蛋白。DR 组肝浸润的 CD20 和 CD8 淋巴细胞频率以及自身抗体的发生率更高。在单变量逻辑回归分析中，诊断时血清γ-谷氨酰转肽酶（GGT）水平，但不是 ALT、Banff 评分或 DSA 的存在，预测了 DR。
在儿童晚期 ACR 治疗中，较高的血清 GGT 水平、自身抗体的存在和 CD8 T 细胞浸润预示着 DR。
