自身抗体
免疫学
表位
医学
抗原
瓜氨酸化
类风湿性关节炎
抗体
B细胞
疾病
自身免疫
生物
遗传学
内科学
瓜氨酸
精氨酸
氨基酸
作者
Hans Ulrich Scherer,Diane van der Woude,René E. M. Toes
标识
DOI:10.1038/s41584-022-00786-4
摘要
The presence of disease-specific autoantibody responses and the efficacy of B cell-targeting therapies in rheumatoid arthritis (RA) indicate a pivotal role for B cells in disease pathogenesis. Important advances have shaped our understanding of the involvement of autoantibodies and autoreactive B cells in the disease process. In RA, autoantibodies target antigens with a variety of post-translational modifications such as carbamylation, acetylation and citrullination. B cell responses against citrullinated antigens generate anti-citrullinated protein antibodies (ACPAs), which are themselves modified in the variable domains by abundant N-linked glycans. Insights into the induction of autoreactive B cells against antigens with post-translational modifications and the development of autoantibody features such as isotype usage, epitope recognition, avidity and glycosylation reveal their relationship to particular RA risk factors and clinical phenotypes. Glycosylation of the ACPA variable domain, for example, seems to predict RA onset in ACPA+ healthy individuals, possibly because it affects B cell receptor signalling. Moreover, ACPA-expressing B cells show dynamic phenotypic changes and develop a continuously proliferative and activated phenotype that can persist in patients who are in drug-induced clinical remission. Together, these findings can be integrated into a conceptual framework of immunological autoreactivity in RA, delineating how it develops and persists and why disease activity recurs when therapy is tapered or stopped.
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