Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Curr Opin Rheumatol. 2012 Jul;24(4):351-8. doi: 10.1097/BOR.0b013e3283534df4.
Spondyloarthritis (SpA) is a chronic immune-mediated inflammatory disease of unknown origin. Here we aim to review whether SpA is driven by T-cell and/or B-cell autoreactivity or by abnormal innate immune responses.
SpA does not share genetic risk factors, female predominance, presence of disease-specific autoantibodies and response to T-cell or B-cell-targeted therapies with prototypical autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Growing evidence indicates that increased responsiveness of innate immune cells such as macrophages, mast cells and neutrophils drives inflammation in SpA. The altered innate immune response may be related to nonantigen-presenting functions of HLA-B27, including the induction of an unfolded protein response, and can be triggered by bacterial and mechanical stress. Innate immune cells appear to be the main producers of both pro-inflammatory (tumor necrosis factor, IL-1, IL-23, IL-17) and anti-inflammatory (IL-10) cytokines in SpA.
The predominance of myeloid above lymphoid alterations suggests an autoinflammatory rather than autoimmune origin of inflammation in SpA. Therefore, targeting innate cells or their inflammatory mediators may be more effective than T-cell or B-cell-directed therapies.
脊柱关节炎（SpA）是一种病因不明的慢性免疫介导性炎症性疾病。本文旨在探讨 SpA 是否由 T 细胞和/或 B 细胞自身反应或异常固有免疫反应引起。
SpA 与典型的自身免疫性疾病如类风湿关节炎（RA）和系统性红斑狼疮（SLE）没有共同的遗传风险因素、女性患病率、疾病特异性自身抗体以及对 T 细胞或 B 细胞靶向治疗的反应。越来越多的证据表明，固有免疫细胞（如巨噬细胞、肥大细胞和中性粒细胞）的反应性增加会驱动 SpA 的炎症。这种改变的固有免疫反应可能与 HLA-B27 的非抗原呈递功能有关，包括诱导未折叠蛋白反应，并且可以由细菌和机械应激触发。固有免疫细胞似乎是 SpA 中促炎（肿瘤坏死因子、IL-1、IL-23、IL-17）和抗炎（IL-10）细胞因子的主要产生者。
髓系改变多于淋巴系改变，提示 SpA 炎症的自身炎症而非自身免疫起源。因此，靶向固有细胞或其炎症介质可能比 T 细胞或 B 细胞靶向治疗更有效。
