多种细胞因子在成人噬血细胞性淋巴组织细胞增生症中的诊断意义。
The diagnostic importance of multiple cytokines in adult hemophagocytic lymphohistiocytosis.
机构信息
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
出版信息
J Clin Lab Anal. 2023 Mar;37(6):e24669. doi: 10.1002/jcla.24669. Epub 2022 Aug 29.
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a category of immunological illnesses that cause out-of-control T cells and macrophages to release life-threatening cytokines. The HLH-2004 diagnostic criteria are the gold standard for HLH diagnosis, but there is a need to investigate the usefulness of various cytokines for HLH diagnosis.
METHODS
Patients admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to December 2020 were included in this retrospective study, with 166 patients with confirmed HLH and 142 febrile patients requiring differential diagnosis completing the sum. Multiplex cytokine assays using multifactor liquid phase microarray technology-based multifactor liquid phase microarray technology were used to detect 33 cytokines. Twenty-eight cytokines detected using the Luminex analytical platform technology were ultimately included in the analysis.
RESULTS
Interleukin-1 receptor antagonist (IL-1 RA), IL-18, interferon-γ (IFN-γ), and interferon-induced protein 10 (IP-10) regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin, growth-related oncogene α (GRO-α), and macrophage inflammatory protein-1 α (MIP-1α) were higher in the HLH group than in the non-HLH group, and the differences were statistically significant. Among them, the area under the curve (AUC) for IL-18 for HLH diagnosis was reported for the first time as 82.69%, with a sensitivity of 76.32% and a specificity of 79.61%; the AUC of IL-1 RA was 72.34%, with a sensitivity of 62.71% and a specificity of 75.97%; and the AUC of IP-10 was 71.73%, with a sensitivity of 60.14% and a specificity of 75.15%. Moreover, the AUC of the combined diagnostic tests for IL-1 RA, IL-18, IFN-γ, IP-10, and RANTES was 99.6%, with a sensitivity of 95.8% and a specificity of 98.6%.
CONCLUSION
Our study concluded that multiple cytokines are valid biological markers for the diagnosis of HLH. The findings of this study remain to be validated in an external dataset.
背景
噬血细胞性淋巴组织细胞增生症（HLH）是一类免疫性疾病，可导致失控的 T 细胞和巨噬细胞释放危及生命的细胞因子。HLH-2004 诊断标准是 HLH 诊断的金标准，但需要研究各种细胞因子在 HLH 诊断中的作用。
方法
本回顾性研究纳入 2016 年 1 月至 2020 年 12 月期间首都医科大学附属北京友谊医院收治的 166 例确诊 HLH 患者和 142 例发热待鉴别患者。采用基于液相芯片技术的多因子液相芯片技术检测 33 种细胞因子，最终纳入分析的有 28 种使用 Luminex 分析平台技术检测的细胞因子。
结果
HLH 组患者白细胞介素-1 受体拮抗剂（IL-1 RA）、IL-18、干扰素-γ（IFN-γ）和干扰素诱导蛋白 10（IP-10）、调节正常 T 细胞表达和分泌的激活因子（RANTES）、嗜酸粒细胞趋化因子（eotaxin）、生长相关癌基因α（GRO-α）和巨噬细胞炎症蛋白-1α（MIP-1α）水平高于非 HLH 组，差异有统计学意义。其中，IL-18 诊断 HLH 的曲线下面积（AUC）首次报道为 82.69%，敏感度为 76.32%，特异度为 79.61%；IL-1 RA 的 AUC 为 72.34%，敏感度为 62.71%，特异度为 75.97%；IP-10 的 AUC 为 71.73%，敏感度为 60.14%，特异度为 75.15%。此外，IL-1 RA、IL-18、IFN-γ、IP-10 和 RANTES 联合诊断试验的 AUC 为 99.6%，敏感度为 95.8%，特异度为 98.6%。
结论
本研究认为多种细胞因子是 HLH 诊断的有效生物标志物。本研究结果有待在外部数据集进一步验证。
Zotero 插件