Neuropeptide Y and dipeptidyl-peptidase IV (CD26) in chronic fatigue syndrome

描述(申请人提供)：根据疾病控制中心(CDC)的病例定义，慢性疲劳综合症(CFS)是一种严重疲劳的疾病，具有明确的相关症状，不能归因于任何其他病理状况。尽管近几年对慢性疲劳综合征的研究有所增加，但对于病因尚未出现一致的意见。目前已经提出了几种病因，免疫、神经内分泌和自主神经，但还没有一致和独特的生理机制与CFS相关。CFS可能包含具有共同症状特征但受不同因素影响的亚群。长期以来，神经肽Y(NPY)等神经肽被认为在炎症性疾病的发病机制中发挥作用。神经肽Y是一种由36个氨基酸组成的神经肽，参与调节心肺、免疫、神经系统和内分泌系统的大量生理和病理生理过程。在外周，NPY集中在交感神经末梢，单独或与儿茶酚胺一起释放。NPY受体存在于免疫系统的大多数细胞中，包括NK细胞。NPY抑制自然杀伤细胞功能(NKCC)。考虑到持续刺激可能产生不利影响，下调机制对神经肽是必不可少的，包括神经肽Y。NPY的一个调节因子是二肽基肽酶IV(CD26)。我们实验室的初步数据显示，淋巴细胞上的CD26浓度异常低。NPY在CFS中的作用尚不明确。我们的目标是提高对CFS病理生理学的理解，开发在诊断、定义亚型和治疗试验中有用的生物标记物。在本研究中，我们将研究CFS神经免疫关系的一个方面。具体目标1是确定与健康、久坐的对照组相比，符合CFS病例定义的患者或部分患者NPY升高的程度。具体目的2是确定与对照组相比，慢性疲劳综合征患者NPY与细胞表面(CD26)浓度的关系。目的3明确NPY和CD26与NKCC在CFS中的关系。目的4：探讨神经肽Y和CD26与慢性疲劳综合征患者病情严重程度的关系。

DESCRIPTION (provided by applicant): According to the Centers for Disease Control (CDC) case definition, Chronic Fatigue Syndrome (CFS) is an illness of severe fatigue with defined associated symptoms that cannot be ascribed to any other pathologic condition. Although studies on CFS have increased in recent years, no unanimity of opinion regarding etiology has emerged. Several etiologies have been proposed, immunological, neuroendocrine, and autonomic, and yet no physiological mechanism has been consistently and uniquely related to CFS. It is probable that CFS encompasses sub-populations that share a common symptom profile yet are mediated by different factors. Neuropeptides such as neuropeptide Y (NPY) have long been proposed to play a role in the pathogenesis of inflammatory diseases. NPY is a 36 amino acid neuropeptide, which participates in the regulation of a large number of physiological and pathophysiological processes in the cardiorespiratory system, immune system, nervous system and endocrine system. In the periphery, NPY is concentrated in the sympathetic nerve endings and is released alone or with catecholamines. NPY receptors are present most cells of the immune system, including NK cells. NPY suppresses natural killer cell function (NKCC). Given the potential for adverse effects with a constant stimulus, down regulation mechanisms are essential for neuropeptides, including NPY. One regulator of NPY is dipeptidyl peptidase IV (CD26). Preliminary data from our lab indicate that CD26 concentrations on lymphocytes are abnormally low. The role of NPY in CFS is undefined. Our goal is to improve the understanding of CFS pathophysiology and to develop biomarkers useful in diagnosis, in defining subsets and in therapeutic trials. In this study, we will study one aspect of the neuroimmune relationship in CFS. Specific Aim 1 is to determine the extent to which patients, or a subset of patients who meet the CFS case definition have elevated NPY, as compared to healthy, sedentary controls. Specific Aim 2 is to determine the relationship of NPY to the cell surface concentration of (CD26) in patients with CFS as compared to controls. Specific Aim 3 is to define the relationship of NPY and CD26 to NKCC in CFS. Specific Aim 4 is to determine the relationship of NPY and CD26 to clinical severity in CFS patients.