Detection, epitope‐mapping and function of anti‐Fas autoantibody in patients with silicosis
Detection, epitope‐mapping and function of anti‐Fas autoantibody in patients with silicosis
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DOI：
10.1111/j.1365-2567.2005.02192.x
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发表时间：
2005-09
期刊：
影响因子：
6.4
通讯作者：
A. Takata-Tomokuni;A. Ueki;M. Shiwa;Y. Isozaki;T. Hatayama;H. Katsuyama;F. Hyodoh;W. Fujimoto;H. Ueki;M. Kusaka;H. Arikuni;T. Otsuki
中科院分区：
文献类型：
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作者：
A. Takata-Tomokuni;A. Ueki;M. Shiwa;Y. Isozaki;T. Hatayama;H. Katsuyama;F. Hyodoh;W. Fujimoto;H. Ueki;M. Kusaka;H. Arikuni;T. Otsuki
通过Fas-Fas配体途径的细胞凋亡失调与自身免疫性疾病的发病相关。由于针对未知抗原的自身抗体存在于这些患者的血清中，因此检查血清样品中是否存在针对Fas分子的自身抗体。采用蛋白质印迹和蛋白质芯片分析，抗Fas的自身抗体检测矽肺，系统性红斑狼疮（SLE）和系统性硬化症（SSc）患者，并在健康人弱检测。采用SPOTs系统对12个氨基酸的多肽进行表位作图，发现最少4个，最多10个表位，表位中有C66、R87、L90、E93和H126等与FasL结合相关的氨基酸残基。来自矽肺患者的含有大量抗Fas自身抗体的血清抑制Fas表达的人细胞系的生长，但不抑制低Fas表达者或Fas基因被小干扰RNA沉默的Fas表达者的生长。Fas胞内区的所有表位均位于死亡结构域。本文讨论了在健康志愿者和矽肺或自身免疫性疾病患者中检测到的抗Fas自身抗体的可能作用。
Dysregulation of apoptosis through the Fas–Fas ligand pathway is associated with the onset of autoimmune disease. Since autoantibodies directed against unknown antigens are present in the sera of these patients, sera samples were examined for the presence of autoantibodies directed against the Fas molecule. Using Western blotting and a ProteinChip analysis, autoantibodies against Fas were detected in patients with silicosis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and weakly detected in healthy individuals. Using epitope mapping employing 12‐amino‐acid polypeptides with the SPOTs system, a minimum of four epitopes and a maximum of 10 epitopes were found. Several amino acid residues involved in binding FasL, such as C66, R87, L90, E93 and H126, were presented within the epitopes. Serum containing a large amount of anti‐Fas autoantibody from silicosis patients inhibited the growth of a Fas‐expressing human cell line, but did not inhibit the growth of a low Fas‐expresser nor a Fas‐expresser in which the Fas gene had been silenced by small interference RNA. All epitopes in the intracellular region of Fas were located in the death domain. The possible roles of anti‐Fas autoantibody detected in healthy volunteers and patients with silicosis or autoimmune diseases are discussed here.