Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment.

Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment.
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DOI:
10.1186/s12967-017-1371-9
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发表时间:
2017-12-29
影响因子:
7.4
通讯作者:
van der Meer JWM
van der Meer JWM
中科院分区:
医学2区
文献类型:
--
作者:
Roerink ME;Knoop H;Bronkhorst EM;Mouthaan HA;Hawinkels LJAC;Joosten LAB;van der Meer JWM

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几十年来,细胞因子紊乱被认为与慢性疲劳综合征/肌痛性脑脊髓炎(CFS/ME)有关。50名女性CFS患者被纳入一项研究,研究白细胞介素-1受体拮抗剂阿那白滞素或安慰剂在4周内的作用。在治疗前和治疗后立即从患者中采集EDTA血浆。在基线时,同时从48名年龄匹配的健康女性邻居对照中收集血浆样本。使用基于“邻近延伸试验”(PEA)的免疫测定法,在1 μL样本中平行测定一组92种炎症标志物。由于转化生长因子β(TGF-β)和白细胞介素-1受体拮抗剂(IL-1 Ra)不包括在该平台中,因此使用ELISA测量这些细胞因子。在CFS/ME患者中,IL-12 p40和CSF-1的“标准化蛋白表达”值显著更高(p值分别为0.0042和0.049)。此外,使用LASSO回归,47个标志物的组合产生了校正AUC为0.73的预测模型。经过多次测试校正后,阿那白滞素对循环细胞因子没有影响。TGF-β在患者和对照组之间没有差异。总之,本研究证明,除了一组预测性生物标志物外,CFS/ME患者中IL-12 p40和CSF-1浓度增加。阿那白滞素对IL-1 Ra以外的循环细胞因子无影响。 试用注册:ClinicalTrials.gov标识符:NCT 02108210,注册日期2014年4月本文的在线版本(10.1186/s12967-017-1371-9)包含补充材料,可供授权用户使用。
Cytokine disturbances have been suggested to be associated with the Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) for decades. Fifty female CFS patients were included in a study on the effect of the interleukin-1-receptor antagonist anakinra or placebo during 4 weeks. EDTA plasma was collected from patients before and directly after treatment. At baseline, plasma samples were collected at the same time from 48 healthy, age-matched female neighborhood controls. A panel of 92 inflammatory markers was determined in parallel in 1 μL samples using a ‘proximity extension assay’ (PEA) based immunoassay. Since Transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) were not included in this platform, these cytokines were measured with ELISA. In CFS/ME patients, the ‘normalized protein expression’ value of IL-12p40 and CSF-1 was significantly higher (p value 0.0042 and 0.049, respectively). Furthermore, using LASSO regression, a combination of 47 markers yielded a prediction model with a corrected AUC of 0.73. After correction for multiple testing, anakinra had no effect on circulating cytokines. TGF-β did not differ between patients and controls. In conclusion, this study demonstrated increased IL-12p40 and CSF-1 concentrations in CFS/ME patients in addition to a set of predictive biomarkers. There was no effect of anakinra on circulating cytokines other than IL-1Ra. Trial Registration: ClinicalTrials.gov Identifier: NCT02108210, Registered April 2014 The online version of this article (10.1186/s12967-017-1371-9) contains supplementary material, which is available to authorized users.
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