Marco-Bonilla Miguel, Fresnadillo Maria, de la Riva-Bueno Macarena, Herrero-Beaumont Gabriel, Largo Raquel, Mediero Aránzazu
Joint and Bone Research Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.
Biology (Basel). 2025 Apr 24;14(5):460. doi: 10.3390/biology14050460.
RA is a chronic autoimmune disease characterized by synovial inflammation and joint damage, driven by autoantibodies such as ACPA, anti-CarP and RF. These autoantibodies, influenced by genetic and environmental factors, play a crucial role in RA pathogenesis through post-translational modifications like citrullination, carbamylation, and acetylation. The early detection of ACPA provides a potential window for intervention, while anti-CarP antibodies correlate with severe disease progression and RF aids in diagnosis. Translating these findings from human pathology to animal models presents significant challenges. Although the presence of adaptative immune cells (T cells) is well defined in animal models of RA, studies yield inconsistent results regarding autoantibody production and implication in the disease onset and progression, with varying detectability of ACPA, anti-CarP antibodies, and RF across different species and models. The collagen-induced arthritis (CIA) model shows PAD4 expression and citrullinated protein presence but inconsistent ACPA detection, while the K/BxN model elucidates the pathogenicity of anti-GPI autoantibodies and implicates Fcγ receptors in disease processes. Therefore, further research is needed to bridge the gap between animal models and human RA pathology. Future studies should focus on developing more representative animal models, exploring pharmacological targets and pathways that involve the interplay between anti-inflammatory and autoimmune responses, and investigating the complex interplay between genetic predisposition, environmental triggers, and autoimmune mechanisms. This approach may lead to improved early diagnostic tools, targeted therapies, and potentially preventive strategies for RA, ultimately enhancing patient outcomes and quality of life.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征为滑膜炎症和关节损伤，由抗环瓜氨酸肽抗体（ACPA）、抗聚角蛋白微丝蛋白抗体（anti-CarP）和类风湿因子（RF）等自身抗体驱动。这些受遗传和环境因素影响的自身抗体，通过瓜氨酸化、氨甲酰化和乙酰化等翻译后修饰，在类风湿性关节炎的发病机制中起关键作用。ACPA的早期检测提供了一个潜在的干预窗口，而anti-CarP抗体与严重的疾病进展相关，RF有助于诊断。将这些人类病理学的发现转化为动物模型存在重大挑战。尽管在类风湿性关节炎动物模型中适应性免疫细胞（T细胞）的存在已得到明确界定，但关于自身抗体产生及其在疾病发作和进展中的作用，研究结果并不一致，不同物种和模型中ACPA、anti-CarP抗体和RF的可检测性也各不相同。胶原诱导的关节炎（CIA）模型显示有肽瓜氨酸化酶4（PAD4）表达和瓜氨酸化蛋白存在，但ACPA检测结果不一致，而K/BxN模型阐明了抗糖基化磷脂酰肌醇（GPI）自身抗体的致病性，并表明Fcγ受体参与疾病过程。因此，需要进一步研究来弥合动物模型与人类类风湿性关节炎病理学之间的差距。未来的研究应专注于开发更具代表性的动物模型，探索涉及抗炎和自身免疫反应相互作用的药理学靶点和途径，并研究遗传易感性、环境触发因素和自身免疫机制之间的复杂相互作用。这种方法可能会带来改进的早期诊断工具、靶向治疗以及潜在的类风湿性关节炎预防策略，最终改善患者的治疗效果和生活质量。
