A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome.

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome.
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DOI:
10.1186/1471-2172-14-29
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发表时间:
2013-06-25
期刊:
影响因子:
3
通讯作者:
Klimas N
Klimas N
中科院分区:
医学4区
文献类型:
--
作者:
Smylie AL;Broderick G;Fernandes H;Razdan S;Barnes Z;Collado F;Sol C;Fletcher MA;Klimas N

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虽然可能与应激反应的基本生理学有关,但我们仍然没有对海湾战争疾病(GWI)的明确认识,这是一种呈现复杂免疫,内分泌和神经症状的衰弱状况。在这里,我们比较了男性(n = 20)和女性(n = 10)退伍军人与GWI分别与他们的健康同行(n = 21男性,n = 9女性),以及受试者与慢性疲劳综合征/肌痛性脑脊髓炎(CFS/ME)(n = 12男性,n = 10女性)。使用分级运动试验(GXT)对受试者进行评估,在运动前、最大运动量(VO 2 max)和运动后4小时抽血。采用荧光显像法测定运动各阶段血浆中IL-1a、1b、2、4、5、6、8、10、12(p70)、13、15、17和23、IFNγ、TNFα和TNFβ的浓度。使用逐步变量选择构建线性分类模型,以鉴定每个受试者组的细胞因子共表达模式特征。使用2至5种细胞因子标记物获得超过80%的分类准确度。IL-10和IL-23表达与GWI和CFS相同,以疾病和时间依赖性方式起作用,在男性受试者中伴随NK和Th 1标志物IL-12、IL-15、IL-2和IFNγ。在女性GWI和CFS受试者中,IL-10再次被鉴定为描绘因子,但这次是在IL-17和Th 2标志物IL-4和IL-5的背景下。运动反应也不同性别之间:男性GWI受试者呈现特征性细胞因子签名在休息,但不是在高峰努力,而女性受试者则相反。虽然个体标记物不同,但结果共同支持IL-23/Th 17/IL-17轴以性别特异性方式参与GWI和CFS的描绘。
Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female). Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group. Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects. Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.
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