Ludwig Institute of Cancer Research, University of Oxford, Oxford, OX3 7DR, UK; Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
J Autoimmun. 2022 Oct;132:102861. doi: 10.1016/j.jaut.2022.102861. Epub 2022 Jul 21.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ inflammatory damage and wide spectrum of autoantibodies. The autoantibodies, especially anti-dsDNA and anti-Sm autoantibodies are highly specific to SLE, and participate in the immune complex formation and inflammatory damage on multiple end-organs such as kidney, skin, and central nervous system (CNS). However, the underlying mechanisms of autoantibody-induced tissue damage and systemic inflammation are still not fully understood. Single cell analysis of autoreactive B cells and monoclonal antibody screening from patients with active SLE has improved our understanding on the origin of autoreactive B cells and the antigen targets of the pathogenic autoantibodies. B cell depletion therapies have been widely studied in the clinics, but the development of more specific therapies against the pathogenic B cell subset and autoantibodies with improved efficacy and safety still remain a big challenge. A more comprehensive autoantibody profiling combined with functional characterization of autoantibodies in diseases development will shed new insights on the etiology and pathogenesis of SLE and guide a specific treatment to individual SLE patients.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征为多器官炎症损伤和广泛的自身抗体谱。自身抗体，特别是抗双链 DNA 和抗 Sm 自身抗体，对 SLE 具有高度特异性，并参与肾脏、皮肤和中枢神经系统（CNS）等多个终末器官的免疫复合物形成和炎症损伤。然而，自身抗体诱导的组织损伤和全身炎症的潜在机制仍未完全阐明。对活动期 SLE 患者的自身反应性 B 细胞进行单细胞分析和单克隆抗体筛选，提高了我们对自身反应性 B 细胞的起源和致病性自身抗体的抗原靶标的认识。B 细胞耗竭疗法已在临床上广泛研究，但开发更针对致病性 B 细胞亚群和具有改善疗效和安全性的自身抗体的特异性疗法仍然是一个巨大的挑战。更全面的自身抗体谱分析结合自身抗体在疾病发展中的功能特征，将为 SLE 的病因和发病机制提供新的见解，并为个体 SLE 患者提供针对性治疗。
