Department of Clinical Immunology, Branch of Immune Cell Biology, State Key Discipline of Cell Biology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an 710032, Shaanxi Province, China; National Translational Science Center for Molecular Medicine, Xi'an 710032, China; Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
Department of Clinical Immunology, Branch of Immune Cell Biology, State Key Discipline of Cell Biology, PLA Specialized Research Institute of Rheumatology & Immunology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an 710032, Shaanxi Province, China; National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
Autoimmun Rev. 2018 Sep;17(9):845-853. doi: 10.1016/j.autrev.2018.02.014. Epub 2018 Jul 11.
The production of anti-citrullinated peptide antibodies (ACPAs) requires the participation of both innate immunity and adaptive immunity. On the one hand, activated innate immunity is able to produce citrullinated auto-antigens that fuel autoimmunity and provide an inflammatory environment that facilitates the breach of self-tolerance, proliferation of self-reactive T/B cells and the production of ACPAs. On the other hand, after their production by plasma B cells, ACPAs are also able to interact with innate immunity to exacerbate the manifestation and chronicity of rheumatoid arthritis (RA). This article discusses the roles of citrullinated peptides and ACPA played in innate immunity and autoimmunity. In addition, we emphasise the relationships between environmental factors and innate immunity, as well as the pathogenic function of ACPAs per se. In doing so, we hope to provide fundamental knowledge of RA pathogenesis and reveal potential therapeutic targets in RA treatment.
抗瓜氨酸化肽抗体(ACPAs)的产生需要先天免疫和适应性免疫的共同参与。一方面,激活的先天免疫能够产生瓜氨酸化自身抗原,从而引发自身免疫,并提供炎症环境,促进自身耐受的破坏、自身反应性 T/B 细胞的增殖以及 ACPA 的产生。另一方面,浆细胞产生 ACPA 后,也能够与先天免疫相互作用,从而加重类风湿关节炎(RA)的表现和慢性化。本文讨论了瓜氨酸肽和 ACPA 在先天免疫和自身免疫中的作用。此外,我们还强调了环境因素与先天免疫之间的关系,以及 ACPA 本身的致病功能。希望通过这些讨论,为 RA 发病机制提供基础知识,并揭示 RA 治疗中的潜在治疗靶点。