高通量测序揭示系统性红斑狼疮B细胞异常的研究进展

High-throughput sequencing technology in the identification of B cell abnormalities in systemic lupus erythematosus

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以致病性自身抗体和免疫复合物形成并介导多器官损伤的急性或慢性自身免疫病,好发于育龄期女性,具有显著异质性。自身反应性B细胞过度活化产生自身抗体是SLE全身免疫病理损伤的重要原因,靶向B细胞治疗SLE的显著疗效提示其在疾病发生和进展中的重要作用。由于自身反应性B细胞参与疾病进展的具体机制和标志分子尚不明确,目前,B细胞耗竭疗法均是针对总的B细胞群体,无法靶向清除自身反应性B细胞。随着科学技术手段的进步,高通量测序技术为研究SLE B细胞异常提供了新思路。本综述重点就高通量测序揭示B细胞受体新的异常、新的B细胞亚群和B细胞相关治疗靶点等在SLE中的作用进展进行总结和讨论,为深入了解SLE的发病机制和探讨治疗方法提供借鉴。

Systemic lupus erythematosus(SLE)is an acute or chronic autoimmune disease characterized by the presence of pathogenic autoantibodies and immune complexes,and multiorgan damage.It is a highly heterogeneous disease and commonly developed in women of childbearing age.The cause of systemic immunopathological injury in SLE is due to the production of autoantibodies by overactivated autoreactive B cells.The treatment of SLE by targeting B cells is very effective,suggesting the critical role of B cells in the development and progression of SLE.However,the current B cell depletion therapies all target the total B cell population,which are not capable of clearing specifically autoreactive B cells since the specific marker molecules and the mechanisms associated with the development of SLE remain unclear.With the development of science and technology,high-throughput sequencing technology provides new ideas for the study of B cell abnormalities in SLE.This review focuses on the progress in high-throughput sequencing to reveal new abnormalities in B cell receptors,new B cell subsets and B cell-related novel therapeutic targets,hoping to provide reference for better understanding the pathogenesis and exploring therapeutic strategies.