Objective: To evaluate the efficacy of rapid immunological indicator-degranulation function (CD107a) and perforin expression in the diagnosis of primary hemophagocytic lymphohistiocytosis (pHLH). Methods: 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). Results: 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 (P<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 (P<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. Conclusions: 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.
目的: 探讨及评价快速免疫学检测指标脱颗粒功能测定(CD107a)及穿孔素(Perforin)表达检测在判定原发性噬血细胞综合征[即原发性噬血细胞性淋巴组织细胞增多症(pHLH)]诊断中的效能。 方法: 回顾性分析2015年4月至2020年6月由首都医科大学附属北京友谊医院、北京京都儿童医院以及首都医科大学附属北京儿童医院三家医疗机构收治的295例行基因筛查的HLH确诊患者的病例资料,对比快速免疫学功能指标CD107a和Perforin表达与基因筛查的契合度,评价两项指标检测的灵敏度、特异度及阳性预测值(PPV)、阴性预测值(NPV),并建立免疫功能学指标对判定pHLH的受试者工作特征(ROC)曲线,选取具有临床指导意义的cut-off值。 结果: 295例HLH患者中,男156例、女139例,年龄2个月~70岁,中位年龄18岁。CD107a检测在判定脱颗粒基因缺陷相关pHLH方面,ROC曲线下面积(AUC)为0.920(P<0.001),约登指数最大时对应的灵敏度为83.3%,特异度为89.2%,PPV为33.3%,NPV为98.8%,cut-off值为7.15%。CD107a>10%在判断不涉及脱颗粒相关基因和基因筛查阴性的患者方面,准确度为81.6%。Perforin表达测定在判定家族性噬血细胞综合征2型(FHL2)方面,在基于实验室正常检测值(≥81%)情况下,该项检测的灵敏度、特异度、PPV和NPV分别为88.2%、64.2%、20.3%和98.1%。建立ROC曲线进一步优化cut-off 值,计算AUC为0.933(P<0.001),约登指数最大值对应的cut-off值为62.34%,此时灵敏度仍保持在88.2%,特异度、PPV和NPV分别提升为91.5%,51.7%和98.7%。 结论: CD107a和Perforin测定对涉及细胞毒功能受损的pHLH具有较好的早期预判意义,选取适当的cut-off值,可为临床精准诊断提供依据。.