Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P?<?0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus.
系统性红斑狼疮（Systemic lupus erythematosus, SLE）是一个复杂的自身免疫性疾病，可产生多种血清自身抗体是SLE主要特征之一。然而，SLE的自身抗体谱尚未被彻底解读。本研究应用一种包含9400种自身抗原的芯片（Protoarray），比较SLE患者与正常人之间自身抗体谱的差别。结果发现：有437种IgG抗体以及1213种IgM抗体在SLE患者血清中的表达显著高于正常人（P<0.05）；并且发现抗细胞核、胞浆及细胞膜的各类新抗体共300个。应用分子间作用网络信息分析发现，这300种新抗体主要作用集中在细胞死亡、细胞周期及DNA修复中。进一步在更大样本量的对列研究中，应用ELISA和Western blot验证了其中一组与细胞凋亡及DNA修复相关的自身抗体（APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S及VRK1），并发现APEX1, HMGB1, VRK1, AURKA, PADI4及SRP19抗体的表达水平与SLE患者抗dsDNA抗体水平呈正相关。应用高通量的芯片方法可有助于发现新的自身抗体，为揭示SLE的发病机制提供依据。





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