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

描述（由申请人提供）：根据疾病控制中心（CDC）病例定义，慢性疲劳综合征（CFS）是一种严重疲劳的疾病，具有定义的相关症状，不能归因于任何其他病理条件。虽然近年来对CFS的研究有所增加，但关于病因学的观点并不一致。已经提出了几种病因学，免疫学，神经内分泌和自主神经，但没有生理机制一直和独特的CFS相关。CFS可能包括具有共同症状特征但由不同因素介导的亚群。神经肽如神经肽Y（NPY）长期以来一直被认为在炎症性疾病的发病机制中发挥作用。NPY是一种由36个氨基酸组成的神经肽，参与心肺系统、免疫系统、神经系统和内分泌系统的大量生理和病理生理过程的调节。在外周，NPY集中在交感神经末梢，并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）。考虑到恒定刺激可能产生不良反应，下调机制对神经肽（包括NPY）至关重要。NPY的一种调节剂是二肽基肽酶IV（CD26）。我们实验室的初步数据表明，淋巴细胞上的CD26浓度异常低。NPY在CFS中的作用尚未明确。我们的目标是提高对CFS病理生理学的了解，并开发用于诊断、定义子集和治疗试验的生物标志物。在本研究中，我们将研究CFS的神经免疫关系的一个方面。具体目标1是确定与健康的久坐对照组相比，符合CFS病例定义的患者或患者子集的NPY升高程度。具体目标2是确定CFS患者与对照组相比NPY与细胞表面（CD26）浓度的关系。具体目标3是明确CFS中NPY和CD 26与NKCC的关系。具体目标4是确定CFS患者中NPY和CD 26与临床严重程度的关系。

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.