Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton’s tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.

系统性红斑狼疮 (SLE) 是一种以多种血清学自身抗体为特征的慢性自身免疫性疾病。抗 dsDNA 抗体参与多器官损伤，尤其是肾脏、皮肤和中枢神经系统。抗 dsDNA 抗体在 SLE 中起着关键作用，研究人员已经开发出针对这些抗体的治疗策略。通过针对 B 细胞表面抗原、B 细胞存活因子或布鲁顿酪氨酸激酶的 B 细胞靶向生物制剂减少抗 dsDNA 抗体的方法有效地消除了 B 细胞。然而，它们的非特异性消耗会阻碍正常的免疫系统功能并限制治疗效果。因此，科学家们尝试了抗 dsDNA 抗体或狼疮特异性策略，例如未成熟的树突状细胞疫苗和免疫吸附。最近，直接阻断抗 dsDNA 自身抗体的合成模拟肽（hCDR1、pCONs、DWEYS、FISLE-412 和 ALW）引起了人们的关注，它可以改善狼疮，降低血清学自身抗体滴度，减少肾脏自身抗体的沉积，改善病理表现. 这些有效的小肽分子具有良好的耐受性、无毒且无免疫原性，已证明具有良好的安全性，有望成为 SLE 管理的有希望的候选药物。在这篇综述中，我们阐明了抗 dsDNA 抗体在 SLE 中的作用，主要关注当前针对抗 dsDNA 抗体的策略，并讨论了它们潜在的临床价值。降低血清学自身抗体滴度，减少肾脏自身抗体沉积，改善病理表现。这些有效的小肽分子具有良好的耐受性、无毒且无免疫原性，已证明具有良好的安全性，有望成为 SLE 管理的有希望的候选药物。在这篇综述中，我们阐明了抗 dsDNA 抗体在 SLE 中的作用，主要关注当前针对抗 dsDNA 抗体的策略，并讨论了它们潜在的临床价值。降低血清学自身抗体滴度，减少肾脏自身抗体沉积，改善病理表现。这些有效的小肽分子具有良好的耐受性、无毒且无免疫原性，已证明具有良好的安全性，有望成为 SLE 管理的有希望的候选药物。在这篇综述中，我们阐明了抗 dsDNA 抗体在 SLE 中的作用，主要关注当前针对抗 dsDNA 抗体的策略，并讨论了它们潜在的临床价值。