山东医药

目的 探讨外周血B淋巴细胞表面程序性死亡受体1(PD-1)、程序性死亡配体1(PD-L1)表达与传染性单核细胞增多症(IM)患儿肝损伤的关系。方法 选取IM患儿203例，检测其入院时外周血B淋巴细胞表面PD-1、PD-L1表达及血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平，以住院期间ALT峰值>40 U/L判定为肝损伤。采用Spearman秩相关分析IM患儿外周血B淋巴细胞表面PD-1与PD-L1表达之间及二者与ALT、AST水平的相关性；比较发生与未发生肝损伤患儿的临床资料，采用多因素Logistic回归分析IM患儿发生肝损伤的独立影响因素；绘制ROC曲线评价PD-1、PD-L1表达单独及联合对IM患儿肝损伤的预测效能。结果 203例IM患儿中，105例发生肝损伤，肝损伤发生率为51.72%。IM患儿外周血B淋巴细胞表面PD-1表达与PD-L1表达呈正相关(r=0.520，P<0.001)；PD-1表达与ALT、AST水平均呈正相关(r分别为0.576、0.547，P均<0.001)；PD-L1表达亦与ALT、AST水平均呈正相关(r分别为0.569、0.563，P均<0.001)。发生肝损伤的IM患儿病程长于未发生肝损伤IM患儿，EBV DNA载量、CRP、CD3⁺ T淋巴细胞比例、CD8⁺ T淋巴细胞比例及外周血B淋巴细胞表面PD-1、PD-L1表达均高于未发生肝损伤患儿，中性粒细胞计数、CD4⁺ T淋巴细胞比例及CD4⁺/CD8⁺均低于未发生肝损伤患儿(P均<0.05)。EBV DNA载量增加、CD3⁺ T淋巴细胞比例升高及PD-1、PD-L1表达升高均为IM患儿发生肝损伤的独立危险因素，CD4⁺/CD8⁺升高为IM患儿发生肝损伤的独立保护因素(P均<0.05)。PD-1、PD-L1表达单独预测IM患儿肝损伤的曲线下面积分别为0.788、0.799，二者联合预测IM患儿肝损伤的曲线下面积为0.908，且联合预测效能高于二者单独预测(P均<0.05)。结论 IM患儿外周血B淋巴细胞表面PD-1、PD-L1表达与ALT、AST水平呈正相关，PD-1、PD-L1表达升高均为IM患儿发生肝损伤的独立危险因素，二者联合检测对IM患儿肝损伤具有一定辅助预测价值。

Objective To investigate the relationship between the surface expression of programme-death receptor 1 (PD-1) and programme-death ligand 1 (PD-L1) on peripheral blood B lymphocytes and liver damage in children with infectious mononucleosis (IM). Methods A total of 203 paediatric patients with infectious mononucleosis (IM) were enrolled. Upon admission， the expression of PD-1 and PD-L1 on the surface of peripheral blood B lymphocytes， as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels， were measured. Liver injury was defined as a peak ALT level >40 U/L during hospitalisation. Spearman’s rank correlation analysis was used to assess the correlation between PD-1 and PD-L1 expression on the surface of peripheral blood B lymphocytes in children with IM， as well as the correlation between these markers and ALT and AST levels; clinical data were compared between children who did and did not develop liver injury; multivariate logistic regression analysis was performed to identify independent risk factors for liver injury in children with IM; and ROC curves were plotted to evaluate the diagnostic performance of PD-1 and PD-L1 expression， both individually and in combination， in predicting liver injury in children with IM. Results Among 203 paediatric patients with IM， 105 developed liver injury， yielding an incidence rate of 51.72%. The surface expression of PD-1 and PD-L1 on peripheral blood B lymphocytes in these patients was positively correlated (r = 0.520， P < 0.001); PD-1 expression was positively correlated with both ALT and AST levels (r = 0.576 and 0.547， respectively; P < 0.001 for both); PD-L1 expression was also positively correlated with both ALT and AST levels (r = 0.569 and 0.563， respectively; P < 0.001 for both). Children with IM who developed liver injury had a longer disease duration than those who did not， and had higher EBV DNA load， CRP， CD3+ T-lymphocyte percentage， CD8+ T-lymphocyte percentage， and PD-1 and PD-L1 expression on the surface of peripheral blood B-lymphocytes compared with those without liver damage; conversely， their neutrophil count， CD4+ T-lymphocyte percentage， and CD4+/CD8+ ratio were lower than in children without liver damage (all P < 0.05). Elevated EBV DNA load， increased CD3+ T-lymphocyte percentage， and elevated PD-1 and PD-L1 expression were all independent risk factors for the development of liver injury in children with IM， whilst an elevated CD4+/CD8+ ratio was an independent protective factor against liver injury in these children (all P < 0.05). The areas under the curve (AUCs) for PD-1 and PD-L1 expression alone in identifying liver injury in children with IM were 0.788 and 0.799， respectively; the AUC for the combined use of PD-1 and PD-L1 was 0.908， and the combined predictive performance was superior to that of either marker alone (all P < 0.05). Conclusion The expression of PD-1 and PD-L1 on the surface of peripheral blood B lymphocytes in children with IM is positively correlated with ALT and AST levels. Elevated expression of both PD-1 and PD-L1 is an independent risk factor for the development of liver injury in children with IM， and the combined detection of these markers has certain auxiliary diagnostic value for identifying liver injury in this paediatric population.