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Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

机译:肌性脑脊髓炎/慢性疲劳综合症(ME / CFS)的免疫特征分析

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A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis. We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature. By combining results from unsupervised and supervised analyses, a candidate immunosignature with 654 peptides was able to differentiate ME/CFS from controls. The immunosignature was tested and further refined using the Norwegian and USA samples. This resulted in a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls in the international data sets. We were able to identify a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation. By extending testing of both our signature and one previously reported in the literature to larger cohorts, and further interrogating the specific peptides we and others have identified, we may deepen our understanding of the origins of ME/CFS and work towards a clinically meaningful diagnostic biomarker.Electronic supplementary materialThe online version of this article (10.1007/s12035-018-1354-8) contains supplementary material, which is available to authorized users.
机译:随机序列肽微阵列可以以广泛,无偏见的方式询问血清抗体,以产生疾病特异性的免疫信号。此方法已应用于癌症检测,感染诊断和疫苗反应询问。我们假设存在一种针对ME / CFS的免疫信号,这可能有助于诊断。我们研究了两个满足ME / CFS加拿大共识定义的主题组。 ME / CFS(n = 25)和匹配的对照(n = 25)血清来自加拿大的一项研究。 ME / CFS(n = 25)血清是从1/2期挪威试验获得的。分析中包括来自美国六个健康对照的血清。对加拿大的病例和对照进行了疾病免疫特征测试。通过结合无监督和无监督分析的结果,具有654种肽的候选免疫签名能够将ME / CFS与对照区分开。使用挪威和美国样品对免疫印记进行了测试并进一步完善。这导致了256肽的免疫签名,能够将ME / CFS病例与国际数据集中的对照区分开。我们能够鉴定出从健康对照组中分离出ME / CFS样品的256肽标记,这提示了免疫功能障碍的即席即跑假说值得进一步研究。通过将我们的签名和先前文献中报道的一项测试扩展到更大的人群,并进一步询问我们和其他人已经鉴定出的特定肽,我们可以加深对ME / CFS起源的了解,并朝着临床上有意义的诊断生物标记物的方向努力电子补充材料本文的在线版本(10.1007 / s12035-018-1354-8)包含补充材料,授权用户可以使用。

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