Classen Jean-François, Henrohn Dan, Rorsman Fredrik, Lennartsson Johan, Lauwerys Bernard R, Wikström Gerhard, Rorsman Charlotte, Lenglez Sandrine, Franck-Larsson Karin, Tomasi Jean-Paul, Kämpe Olle, Vanthuyne Marie, Houssiau Frédéric A, Demoulin Jean-Baptiste
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Arthritis Rheum. 2009 Apr;60(4):1137-44. doi: 10.1002/art.24381.
Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc.
Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center.
Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal.
The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.
系统性硬化症（SSc）是一种病因不明的严重结缔组织疾病，其特征为皮肤和多个内脏器官的纤维化。最近的研究结果表明，该疾病由针对血小板衍生生长因子受体（PDGFR）的刺激性自身抗体驱动，这些抗体刺激成纤维细胞产生活性氧（ROS）和胶原蛋白。这些结果为SSc的诊断和治疗开辟了新的研究途径。本研究旨在证实SSc患者中抗PDGFR抗体的存在。
通过蛋白A/G层析法纯化37例SSc患者的免疫球蛋白。使用4种不同的灵敏生物测定法检测PDGFR的激活情况，即细胞增殖、ROS产生、信号转导和受体磷酸化；后者也在来自不同研究中心的另外7例SSc患者中进行了检测。
对SSc患者纯化的IgG样本进行抗核自身抗体检测时呈阳性，但在任何检测中均未特异性激活PDGFRα或PDGFRβ。用血小板衍生生长因子（PDGF）本身刺激细胞始终产生强烈信号。
目前的结果对SSc中是否存在针对PDGFR的激动性自身抗体提出了疑问。
