儿童异基因造血干细胞移植后血浆sST2/Reg3α蛋白水平与急性移植物抗宿主病的相关性

The Relationship between Plasma sST2/Reg3α Levels and Acute Graft-Versus-Host Disease in Children After Allogeneic Hematopoietic Stem Cell Transplantation

目的:探讨儿童异基因造血干细胞移植(allo-HSCT)后血浆sST2/Reg3α蛋白动态变化与急性移植物抗宿主病(aGVHD)的相关性。方法:收集2019年1月至2020年1月在武汉儿童医院血液肿瘤科接受allo-HSCT的患儿29例的临床资料。采集患者移植后14 d和28 d外周血标本,使用Luminex方法检测血浆sST2/Reg3α蛋白浓度。结果:29例患儿中男性15例,女性14例,中位年龄53(29-117)个月。接受移植后0-I度aGVHD 18例,II-IV度aGVHD11例;皮肤aGVHD 6例,肠道aGVHD(GI-aGVHD)3例,肠道及皮肤aGVHD 5例。II-IV度aGVHD组与0-I度aGVHD组移植后28 d血浆sST2蛋白水平分别为101.81(73.94-150.77)ng/ml与48.97(28.82-56.69)ng/ml,差异具有统计学意义(P=0.021)。GI-aGVHD组与无aGVHD组患者移植后28 d血浆sST2蛋白水平分别为118.74(87.00-243.36)ng/ml和48.97(23.55-61.40) ng/ml,差异具有显著性(P=0.004)。当移植后28 d血浆sST2蛋白浓度≥65.34ng/ml时预测II-IV度aGVHD的敏感度为85.7%,特异性为87.5%;且移植后血浆sST2蛋白高水平组(≥65.34 g/ml)患者II-IV度aGVHD发生率显著高于低水平组(<65.34 ng/ml)(P=0.021)。Reg3α蛋白在II-IV度aGVHD组与无aGVHD组的差异无统计学意义。结论:儿童allo-HSCT后血浆sST2蛋白水平升高提示II-IV度aGVHD的发生。高水平sST2蛋白有望作为预测II-IV度aGVHD发生的生物学诊断标志。

Objective: To explore the relationship between plasma sST2/Reg3α levels and acute graft-versushost disease(aGVHD) in children after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods:The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children′s Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay. Results: Among 29 patients there were 15 males and 14 females with a median age of 53(29-117) months.After allo-HSCT, 18 patients developed grade 0-I aGVHD;while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD(GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81(73.94-150.77) ng/ml vs 48.97(28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74(87.00-243.36) ng/ml vs 48.97(23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥ 65.34 ng/ml at 28 days after alloHSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of< 65.34 ng/ml after allo-HSCT(P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones. Conclusion: The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.