Zhang J, Sun Y, Zhang R, Xiao J, Wang J S, Wu L, Song Y, Wang Z
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Department of Hematology, Beijing Jingdu Children's Hospital, Beijing 102208, China.
Zhonghua Yi Xue Za Zhi. 2022 Jul 26;102(28):2161-2166. doi: 10.3760/cma.j.cn112137-20220221-00346.
To evaluate the efficacy of rapid immunological indicator-degranulation function (CD107a) and perforin expression in the diagnosis of primary hemophagocytic lymphohistiocytosis (pHLH). The clinical data of 295 HLH patients who underwent genetic screening from April 2015 to June 2020 in Beijing Friendship Hospital, Capital Medical University, Beijing Jingdu Children's Hospital and Beijing Children's Hospital, Capital Medical University was collected and analyzed. The fitness of CD107a and Perforin expression with genetic screening was compared to evaluate the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of the two indicators, and the receiver operating characteristic (ROC) curves were generated and used to determine the optimal threshold (cut-off values) of CD107a and Perforin expression assays that would identify pHLH patients with a maximum sensitivity and specificity (Youden index). In all 295 patients included, there were 156 males and 139 females, aged from 2 months to 70 years, with a median age of 18 years. In terms of distinguishing the type of pHLH associated with degranulation gene defect from all other genetic screening results, in the CD107a testing, the ROC curve was generated and showed an area under the curve (AUC) of 0.920 (<0.001), and the optimal cut-off value was determined to be 7.15% with a sensitivity of 83.3% and specificity of 89.2% when the corresponding Youden index was maximized. The PPV and NPV were 33.3% and 98.8%, respectively. CD107a>10% had an accuracy of 81.6% in judging patients without degranulation-related gene defect and negative genetic screening results. In addition, in terms of distinguishing the type of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) from all other genetic screening results, the sensitivity, specificity, PPV and NPV of the Perforin expression testing were 88.2%, 64.2%, 20.3% and 98.1%, respectively, based on the normal laboratory test value (≥ 81%). The ROC curve was established to further optimize the cut-off value. The AUC was 0.933 (<0.001). The cut-off value corresponding to the maximum Youden index was 62.34%, and the sensitivity remained at 88.2%. While the specificity, PPV and NPV rose to 91.5%, 51.7% and 98.7%, respectively. CD107a and Perforin assays have good significance of early prediction for pHLH involved in impaired cytotoxic function. Selecting appropriate cut-off values can provide basis for accurate clinical diagnosis.
评估快速免疫指标——脱颗粒功能（CD107a）和穿孔素表达在原发性噬血细胞性淋巴组织细胞增生症（pHLH）诊断中的效能。收集并分析了2015年4月至2020年6月期间在北京友谊医院、首都医科大学附属北京京都儿童医院和首都医科大学附属北京儿童医院接受基因筛查的295例HLH患者的临床资料。比较CD107a和穿孔素表达与基因筛查的拟合度，以评估这两个指标的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV），并绘制受试者工作特征（ROC）曲线，用于确定能以最大敏感性和特异性（约登指数）识别pHLH患者的CD107a和穿孔素表达检测的最佳阈值（临界值）。纳入的295例患者中，男性156例，女性139例，年龄从2个月至70岁，中位年龄18岁。在区分与脱颗粒基因缺陷相关的pHLH类型与所有其他基因筛查结果方面，在CD107a检测中，绘制的ROC曲线显示曲线下面积（AUC）为0.920（<0.001），当相应的约登指数最大化时，确定最佳临界值为7.15%，敏感性为83.3%，特异性为89.2%。PPV和NPV分别为33.3%和98.8%。CD107a>10%在判断无脱颗粒相关基因缺陷且基因筛查结果为阴性的患者时准确率为81.6%。此外，在区分2型家族性噬血细胞性淋巴组织细胞增生症（FHL2）类型与所有其他基因筛查结果方面，基于正常实验室检测值（≥81%），穿孔素表达检测的敏感性、特异性、PPV和NPV分别为88.2%、64.2%、20.3%和98.1%。建立ROC曲线以进一步优化临界值。AUC为0.933（<0.001）。对应最大约登指数的临界值为62.34%，敏感性保持在88.2%。而特异性、PPV和NPV分别升至91.5%、51.7%和98.7%。CD107a和穿孔素检测对涉及细胞毒性功能受损的pHLH具有良好的早期预测意义。选择合适的临界值可为准确的临床诊断提供依据。
