靶向抗dsdna抗体治疗SLE的策略

IF 8.4 2区 医学 Q1 ALLERGY
Yaqi Wang, Shengxiang Xiao, Yumin Xia, Huixia Wang
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引用次数: 10

摘要

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抗体涉及多器官损伤,特别是肾脏、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抗体的方法已经有效地消除了B细胞。然而,它们的非特异性消耗阻碍了正常的免疫系统功能,限制了治疗效果。因此,科学家们尝试了抗dsdna抗体或狼疮特异性策略,如未成熟树突状细胞疫苗和免疫吸附。近年来,人工合成的直接阻断抗dsdna自身抗体的模拟肽(hCDR1、pCONs、DWEYS、FISLE-412、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、无毒和非免疫原性,已被证明具有良好的安全性,有望成为SLE治疗的有希望的候选药物。在本文中,我们阐明了抗dsdna抗体在SLE中的作用,重点介绍了目前针对抗dsdna抗体的策略,并讨论了其潜在的临床价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies.

The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies.

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.

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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
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