Mo Shouqi, Li Yilan, He Junbing, Lin Ling
Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Department of Rheumatology, Jieyang People's Hospital, Jieyang, China.
Front Med (Lausanne). 2024 Oct 4;11:1472019. doi: 10.3389/fmed.2024.1472019. eCollection 2024.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical manifestations, often leading to significant morbidity and mortality, particularly due to lupus nephritis (LN). The standard therapeutic approach involving mycophenolate mofetil, cyclophosphamide, and glucocorticoids has shown limitations due to cumulative toxicity and side effects. The introduction of biologic agents, especially rituximab (RTX), a chimeric monoclonal antibody targeting CD20+ B cells, has revolutionized the treatment landscape. This review synthesized the current understanding of B cells' role in SLE and LN and evaluates RTX's therapeutic impact. B cells contribute to disease pathogenesis through autoantibody production and immune complex formation, leading to tissue damage. RTX's mechanisms of action, including Complement-Dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis, have demonstrated efficacy in both SLE and LN treatment. Clinical studies have reported remission rates and improved renal outcomes with RTX use, although challenges such as human anti-chimeric antibody development and optimal dosing persist. The review emphasized the need for continued research to elucidate RTX's long-term benefits and risks, and to explore personalized treatment strategies that incorporate B cell biology for better disease management in SLE and LN.
系统性红斑狼疮(SLE)是一种临床表现多样的慢性自身免疫性疾病,常导致显著的发病率和死亡率,尤其是狼疮性肾炎(LN)所致。包括霉酚酸酯、环磷酰胺和糖皮质激素在内的标准治疗方法,由于累积毒性和副作用已显示出局限性。生物制剂的引入,特别是利妥昔单抗(RTX),一种靶向CD20+B细胞的嵌合单克隆抗体,彻底改变了治疗格局。本综述综合了目前对B细胞在SLE和LN中的作用的理解,并评估了RTX的治疗效果。B细胞通过产生自身抗体和形成免疫复合物导致组织损伤,从而促进疾病发病机制。RTX的作用机制,包括补体依赖性细胞毒性(CDC)、抗体依赖性细胞介导的细胞毒性(ADCC)和诱导凋亡,已在SLE和LN治疗中显示出疗效。临床研究报告了使用RTX后的缓解率和改善的肾脏结局,尽管诸如人抗嵌合抗体产生和最佳剂量等挑战仍然存在。该综述强调需要持续研究以阐明RTX的长期益处和风险,并探索结合B细胞生物学的个性化治疗策略,以便在SLE和LN中更好地管理疾病。