Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis.

Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis.
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DOI:
10.1186/s13075-021-02644-2
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发表时间:
2021-10-15
影响因子:
4.9
通讯作者:
Kawakami A
Kawakami A
中科院分区:
医学2区
文献类型:
--
作者:
Koga T;Furukawa K;Migita K;Morimoto S;Shimizu T;Fukui S;Umeda M;Endo Y;Sumiyoshi R;Kawashiri SY;Iwamoto N;Ichinose K;Tamai M;Origuchi T;Maeda T;Yachie A;Kawakami A

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鉴定潜在的生物标志物,以区分家族性地中海热(FMF)和败血症。我们招募了28名诊断为典型FMF的患者(根据Tel Hashomer标准),22名脓毒症患者和118名年龄匹配的对照组。采用多悬浮细胞因子阵列分析血清40种细胞因子水平。我们对FMF组和脓毒症组中的每个细胞因子进行了聚类分析,以确定特定的分子网络。采用多变量分类(随机森林分析)和logistic回归分析对细胞因子的重要性进行排序,并确定区分FMF和败血症的特异性生物标志物。40种细胞因子中有15种适合进一步分析。FMF患者血清粒细胞-巨噬细胞集落刺激因子(GM-CSF)、成纤维细胞生长因子2、血管内皮生长因子、巨噬细胞炎症蛋白-1b和白细胞介素-17水平显著升高,而肿瘤坏死因子-α (TNF-α)水平显著低于脓毒症患者。细胞因子聚类模式在两组之间存在差异。多因素分类后的logistic回归分析显示,GM-CSF和TNF-α均能准确区分FMF和败血症(GM-CSF的临界值为8.3 pg/mL; TNF-α = 16.3 pg/mL;敏感性92.9%;特异性94.4%;准确性93.4%)。基于多种细胞因子的测量,联合测定GM-CSF和TNF-α水平可能是FMF与败血症鉴别诊断的生物标志物。在线版本包含补充材料,可在10.1186/s13075-021-02644-2获得。
To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis. We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis. Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%). Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines. The online version contains supplementary material available at 10.1186/s13075-021-02644-2.
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