Moura Rita A, Fonseca João Eurico
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisbon Academic Medical Centre, Lisbon, Portugal.
Front Med (Lausanne). 2022 Apr 4;9:851532. doi: 10.3389/fmed.2022.851532. eCollection 2022.
Juvenile idiopathic arthritis (JIA) is a term that collectively refers to a group of chronic childhood arthritides, which together constitute the most common rheumatic condition in children. The International League of Associations for Rheumatology (ILAR) criteria define seven categories of JIA: oligoarticular, polyarticular rheumatoid factor (RF) negative (RF-), polyarticular RF positive (RF+), systemic, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. The ILAR classification includes persistent and extended oligoarthritis as subcategories of oligoarticular JIA, but not as distinct categories. JIA is characterized by a chronic inflammatory process affecting the synovia that begins before the age of 16 and persists at least 6 weeks. If not treated, JIA can cause significant disability and loss of quality of life. Treatment of JIA is adjusted according to the severity of the disease as combinations of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and/ or biological disease modifying anti-rheumatic drugs (DMARDs). Although the disease etiology is unknown, disturbances in innate and adaptive immune responses have been implicated in JIA development. B cells may have important roles in JIA pathogenesis through autoantibody production, antigen presentation, cytokine release and/ or T cell activation. The study of B cells has not been extensively explored in JIA, but evidence from the literature suggests that B cells might have indeed a relevant role in JIA pathophysiology. The detection of autoantibodies such as antinuclear antibodies (ANA), RF and anti-citrullinated protein antibodies (ACPA) in JIA patients supports a breakdown in B cell tolerance. Furthermore, alterations in B cell subpopulations have been documented in peripheral blood and synovial fluid from JIA patients. In fact, altered B cell homeostasis, B cell differentiation and B cell hyperactivity have been described in JIA. Of note, B cell depletion therapy with rituximab has been shown to be an effective and well-tolerated treatment in children with JIA, which further supports B cell intervention in disease development.
幼年特发性关节炎（JIA）是一个统称，指一组儿童慢性关节炎，它们共同构成儿童中最常见的风湿性疾病。国际风湿病联盟（ILAR）标准定义了JIA的七种类别：少关节型、多关节型类风湿因子（RF）阴性（RF-）、多关节型RF阳性（RF+）、全身型、附着点炎相关关节炎、银屑病关节炎和未分化关节炎。ILAR分类将持续性和扩展性少关节炎列为少关节型JIA的子类别，而非独立类别。JIA的特征是在16岁之前开始并持续至少6周的影响滑膜的慢性炎症过程。如果不进行治疗，JIA可导致严重残疾和生活质量下降。JIA的治疗根据疾病严重程度进行调整，采用非甾体类抗炎药（NSAIDs）、合成和/或生物改善病情抗风湿药（DMARDs）的联合使用。尽管疾病病因尚不清楚，但固有免疫和适应性免疫反应的紊乱与JIA的发生有关。B细胞可能通过自身抗体产生、抗原呈递、细胞因子释放和/或T细胞激活在JIA发病机制中发挥重要作用。JIA中对B细胞的研究尚未广泛开展，但文献证据表明B细胞可能确实在JIA病理生理学中发挥相关作用。JIA患者中抗核抗体（ANA）、RF和抗瓜氨酸化蛋白抗体（ACPA）等自身抗体的检测支持B细胞耐受性的破坏。此外，JIA患者外周血和滑液中已记录到B细胞亚群的改变。事实上，JIA中已描述了B细胞稳态、B细胞分化和B细胞过度活跃的改变。值得注意的是，利妥昔单抗的B细胞清除疗法已被证明是JIA儿童有效且耐受性良好的治疗方法，这进一步支持了B细胞干预在疾病发展中的作用。
