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.

中文翻译：

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与系统性红斑狼疮中细胞死亡和DNA修复途径相关的新型自身抗体。

系统性红斑狼疮（SLE）是一种复杂的自身免疫综合症，其特征是患者血液中存在多种共存的自身抗体（autoAbs）。但是，尚未全面阐明SLE中的autoAb的全谱。在这项研究中，使用载有9400抗原的商业平台（ProtoArray）来鉴定SLE患者血清中显着升高的autoAb。通过比较SLE患者和健康对照者的autoAb谱，我们鉴定出437个IgG和1213 IgM autoAb，它们在SLE中的表达水平显着增加（P <0.05）。ProtoArray平台的使用发现了300多种针对多种核，细胞质和膜抗原的新型自动抗体。分子相互作用网络分析表明，autoAb靶向的抗原在细胞死亡，细胞周期和DNA修复途径中最丰富。ELISA和Western blot进一步验证了与细胞凋亡和DNA修复功能相关的一组autoAb，包括针对APEX1，AURKA，POLB，AGO1，HMGB1，IFIT5，MAPKAPK3，PADI4，RGS3，SRP19，UBE2S和VRK1的抗体。更大的队列。此外，SLE患者中针对APEX1，HMGB1，VRK1，AURKA，PADI4和SRP19的autoAbs水平与抗dsDNA水平呈正相关。全面的autoAb筛选已鉴定出新颖的autoAb，它可能揭示导致狼疮的潜在病原体途径。包括针对APEX1，AURKA，POLB，AGO1，HMGB1，IFIT5，MAPKAPK3，PADI4，RGS3，SRP19，UBE2S和VRK1的那些，通过ELISA和Western blot在更大的队列中进一步验证。此外，SLE患者中针对APEX1，HMGB1，VRK1，AURKA，PADI4和SRP19的autoAbs水平与抗dsDNA水平呈正相关。全面的autoAb筛选已鉴定出新颖的autoAb，可以揭示导致狼疮的潜在致病途径。包括针对APEX1，AURKA，POLB，AGO1，HMGB1，IFIT5，MAPKAPK3，PADI4，RGS3，SRP19，UBE2S和VRK1的那些，通过ELISA和Western blot在更大的队列中进一步验证。此外，SLE患者中针对APEX1，HMGB1，VRK1，AURKA，PADI4和SRP19的autoAbs水平与抗dsDNA水平呈正相关。全面的autoAb筛选已鉴定出新颖的autoAb，可以揭示导致狼疮的潜在致病途径。