Orosomucoid (ORM) as a Potential Biomarker for the Diagnosis of Chronic Fatigue Syndrome (CFS)
Orosomucoid (ORM) as a Potential Biomarker for the Diagnosis of Chronic Fatigue Syndrome (CFS)
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Orosumucoid (ORM) 作为诊断慢性疲劳综合征 (CFS) 的潜在生物标志物
DOI：
10.1111/cns.12522
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Sun Y;Zhang ZX;Liu X
慢性疲劳综合征（CFS）是一种以持续至少6个月的不明原因疲劳为特征的疾病，这种疲劳无法通过休息来缓解，它会影响身体的各个系统，导致认知问题，肌肉疼痛，睡眠问题等。体力或精神活动会加重这种疾病。CFS是一个普遍存在的问题，CFS的患病率估计值从0.007%到2.8%不等[1]。目前，CFS的诊断通常依赖于主观的自我报告的感觉，只有当其他疲劳病因被排除后才能做出诊断。例如，诊断CFS的常用标准包括头痛，多个关节或肌肉疼痛，记忆力受损，注意力集中和睡眠。然而，这些情况也经常与其他心理社会因素有关，如睡眠障碍，抑郁和焦虑[2，3]。因此，寻找CFS相关的特征性生物标志物对提高CFS的诊断和治疗水平至关重要。Orosomucoid（ORM）是一种急性噬菌体蛋白，具有多种生物学活性，包括调节免疫、携带药物、维持毛细血管屏障功能、介导鞘脂代谢以及作为疾病标志物[4]。在我们之前的研究中，我们发现ORM在各种形式的疲劳啮齿动物的血清中显著上调，特别是在CFS研究中使用的睡眠剥夺大鼠中占主导地位[5，6]。为了探讨ORM是否可以作为CFS的生物标志物，我们检测了46名根据CDC诊断标准诊断为CFS的患者[7]和38名健康志愿者的血清ORM水平。与来自健康志愿者的血清（0.44 mg/mL）相比，在来自CFS患者的血清（2.78 mg/mL）中发现显著升高的ORM水平（图1A）。来自志愿者的血清中的ORM水平均低于lmg/mL，而来自46名CFS个体中的45名的血清含有高于lmg/mL的ORM水平（图1B）。已知糖皮质激素是ORM表达的主要调节剂。然而，这些CFS患者的血清皮质醇水平中度降低（图2），这与先前报告CFS患者轻度皮质醇减少的研究一致，表明临床相关的下丘脑-垂体-肾上腺（HPA）轴功能障碍[8]。这些结果表明，ORM增加不是应激反应的直接结果。疲劳是一种常见的，但非特异性和高度主观的症状。疲劳的检测和评估是社会生活和临床实践中的一项常见任务。目前，仍然没有与CFS一致相关的特定因素，也没有官方或半官方的CFS治疗建议[9]。我们在图1中发现了慢性疲劳综合征患者的血清ORM水平。来自38名健康志愿者（对照）和46名诊断患有CFS的个体的血清中的ORM水平。数据为平均值SD。*P < 0.05，通过学生t检验。
Chronic fatigue syndrome (CFS) is an illness characterized by unexplained fatigue lasting at least 6 months that is not relieved by rest, which affects different body systems and results in cognitive problems, muscle pains, sleep problems, and so on. Physical or mental activity could worsen this illness. CFS is a widespread problem, and estimate for the prevalence of CFS varies widely from 0.007% to 2.8% [1]. At present, diagnosis of CFS usually depends on subjective self-reported feeling and can be made only when other etiologies of fatigue have been excluded. For example, the commonly used criteria for diagnosing CFS include headache, pain in multiple joints or muscles, impaired memory, concentration, and sleep. However, these conditions are also frequently associated with other psychosocial factors, such as sleep disorder, depression, and anxiety [2,3]. Therefore, discovering associated characteristic biomarkers are essential for improving the diagnosis and treatment of CFS. Orosomucoid (ORM) is an acute phage protein which has many biological activities including modulating immunity, carrying drugs, maintaining the barrier function of capillary, mediating the sphingolipid metabolism, and also acting as an disease marker [4]. In our previous study, we found that ORM was significantly upregulated in serum of various forms of fatigued rodents, especially dominantly in sleep-deprivation rats which have been used in the study of CFS [5,6]. To explore whether ORM could be utilized as a biomarker for CFS, we examined the serum level of ORM in 46 patients diagnosed with CFS according to CDC diagnosis criteria [7] and a group of 38 healthy volunteers. A significantly elevated level of ORM was found in sera from CFS patients (2.78 mg/mL) compared with that from healthy volunteers (0.44 mg/mL) (Figure 1A). The levels of ORM in sera from the volunteers are all lower than 1 mg/mL, whereas sera from 45 of the 46 CFS individuals contain ORM level higher than 1 mg/mL (Figure 1B). Glucocorticoids are known as a major regulator of ORM expression. However, the serum cortisol level in these CFS patients was moderately decreased (Figure 2),which is in accordance previous studies which reported mild hypocortisolism in CFS patients indicating clinically relevant hypothalamic–pituitary–adrenal (HPA) axis dysfunction [8]. These findings indicated that the ORM increase is not a direct result of stress response. Fatigue is a commonly experienced, but nonspecific and highly subjective symptom. Detecting and evaluating fatigue is a common task both in various society activities and in clinical practice. At present, there are still no specific factors that have been consistently associated with CFS, and there are no official or semi-official recommendations for the treatment of CFS [9]. We found in Figure 1 Serum ORM level in individuals with chronic fatigue syndrome. ORM level in sera from 38 healthy volunteers (control) and 46 individuals diagnosed with CFS. Data are mean SD. *P < 0.05, by Student’s t-test.
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