Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo 113-8603, Japan.
Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Organization for Research, Shimane University, Izumo, Shimane 693-8501, Japan.
Int J Mol Med. 2016 Feb;37(2):461-7. doi: 10.3892/ijmm.2015.2437. Epub 2015 Dec 18.
Joint hypermobility syndrome (JHS) (also termed Ehlers-Danlos syndrome, hypermobility type) is a heritable connective tissue disorder which is characterized by generalized joint hypermobility, chronic pain, dizziness, fatigue, and minor skin changes. However, it has yet to be determined in patients with JHS whether specific genetic factors are involved in the risk of developing the disorder. Therefore, interventions have been limited to symptomatic treatments, and biomarkers for diagnosis and therapy have not yet been identified. In the present study, to identify potential serum biomarkers for JHS, we examined proteins with differential levels in sera from patients with JHS and in sera from control individuals using isobaric tags for relative and absolute quantitation (iTRAQ) labeling in combination with nano LC-MALDI-TOF/TOF-MS/MS followed by ProteinPilot analysis. In the sera of patients with JHS, a total of 106 proteins with differential levels were identified, and they were further narrowed down to 6 proteins (p<0.05, patient vs. control). Of the 6 proteins, proteins involved in the complement system including complement C1r subcomponent (C1R), vitronectin (VTN), complement component C9 (C9), and C4b-binding protein alpha chain (C4BPA) were identified as increased proteins in sera from patients with JHS compared with those in sera from controls. We confirmed increased levels of C1R and VTN in sera from patients with JHS by western blot analyses. The results indicate the possibility of a locally occurring inflammatory process in patients with JHS.
关节过度活动综合征（JHS）（也称为埃勒斯-当洛斯综合征，过度活动型）是一种遗传性结缔组织疾病，其特征为广泛的关节过度活动、慢性疼痛、头晕、疲劳和轻微的皮肤变化。然而，在 JHS 患者中尚未确定是否存在特定的遗传因素会增加发病风险。因此，干预措施仅限于对症治疗，且尚未确定用于诊断和治疗的生物标志物。在本研究中，为了鉴定 JHS 的潜在血清生物标志物，我们使用相对和绝对定量同位素标记（iTRAQ）标记联合纳升液相色谱-基质辅助激光解吸/电离飞行时间/飞行时间质谱（nano LC-MALDI-TOF/TOF-MS/MS），结合 ProteinPilot 分析，检测了 JHS 患者和对照个体血清中差异表达的蛋白。在 JHS 患者的血清中，共鉴定到 106 种差异表达蛋白，并进一步缩小到 6 种蛋白（p<0.05，患者与对照）。在这 6 种蛋白中，补体系统中涉及的蛋白，包括补体 C1r 亚单位（C1R）、纤连蛋白（VTN）、补体成分 C9（C9）和 C4 结合蛋白 α 链（C4BPA），被鉴定为 JHS 患者血清中较对照血清中增加的蛋白。我们通过 Western blot 分析证实了 JHS 患者血清中 C1R 和 VTN 水平的增加。结果表明 JHS 患者体内可能存在局部炎症过程。
