The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies.
The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies.
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DOI：
10.1007/s12016-021-08898-7
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发表时间：
2022-10
影响因子：
9.1
通讯作者：
Wang, Huixia
中科院分区：
文献类型：
--
作者：
Wang, Yaqi;Xiao, Shengxiang;Xia, Yumin;Wang, Huixia
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抗体与多器官损伤有关，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细胞生存因子或Bruton‘s酪氨酸激酶的B细胞靶向生物制剂来降低抗dsDNA抗体的方法已经有效地消除了B细胞。然而，它们的非特异性耗竭阻碍了正常的免疫系统功能，并限制了治疗益处。因此，科学家们尝试了抗dsDNA抗体或狼疮特异性策略，如未成熟的树突状细胞疫苗和免疫吸附。近年来，人工合成的模拟多肽(hCDR1、pCONs、DWEYS、FISLE-412和ALW)可直接封闭抗双链DNA自身抗体，具有改善狼疮、降低血清学自身抗体滴度、减少肾脏自身抗体沉积、改善病理变化等作用，近年来受到广泛关注。这些有效的小肽分子耐受性好，无毒，无免疫原性，已显示出良好的安全性，有望成为SLE治疗的候选药物。本文就抗dsDNA抗体在系统性红斑狼疮中的作用作一综述，重点介绍目前针对抗dsDNA抗体的策略，并讨论其潜在的临床价值。
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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DOI：
10.1002/art.39856
发表时间：
2017-02
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Clowse ME;Wallace DJ;Furie RA;Petri MA;Pike MC;Leszczyński P;Neuwelt CM;Hobbs K;Keiserman M;Duca L;Kalunian KC;Galateanu C;Bongardt S;Stach C;Beaudot C;Kilgallen B;Gordon C;EMBODY Investigator Group
通讯作者：
EMBODY Investigator Group
影响因子：
27.4
作者：
Bertsias GK;Tektonidou M;Amoura Z;Aringer M;Bajema I;Berden JH;Boletis J;Cervera R;Dörner T;Doria A;Ferrario F;Floege J;Houssiau FA;Ioannidis JP;Isenberg DA;Kallenberg CG;Lightstone L;Marks SD;Martini A;Moroni G;Neumann I;Praga M;Schneider M;Starra A;Tesar V;Vasconcelos C;van Vollenhoven RF;Zakharova H;Haubitz M;Gordon C;Jayne D;Boumpas DT;European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association
通讯作者：
European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association
影响因子：
--
作者：
Emery, P;Fleischmann, R;Shaw, TM
通讯作者：
Shaw, TM
全身性红斑狼疮期间，B细胞中的Toll样受体信号传导。
DOI：
10.1038/s41584-020-00544-4
发表时间：
2021-03
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Fillatreau S;Manfroi B;Dörner T
通讯作者：
Dörner T
影响因子：
158.5
作者：
Furie, Richard;Rovin, Brad H.;Roth, David A.
通讯作者：
Roth, David A.