Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity. EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0–57), and pain levels were measured using a visual analogue scale (VAS, 0–10 cm). Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group. The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.

中文翻译：

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幼年特发性关节炎儿童的血脑屏障通透性和星形胶质细胞衍生的细胞外囊泡：一项横断面研究

幼年特发性关节炎 (JIA) 是儿童中最常见的风湿性疾病，其炎症过程已得到广泛研究，其主要特征是其对关节健康的影响。新的证据表明，幼年特发性关节炎也可能影响中枢神经系统 (CNS)。本研究通过分析血浆中星形胶质细胞来源的细胞外囊泡 (EV) 和 S100B 蛋白的存在来研究 JIA 中潜在的中枢神经系统参与，这两者都表明星形胶质细胞活性和血脑屏障 (BBB) 完整性。通过流式细胞术测量 90 名诊断为 JIA 的儿童和 10 名健康对照者的 EDTA 血浆（按年龄和性别匹配），分析细胞外囊泡。使用流式细胞术和水通道蛋白 4 (AQP-4) 和胶质纤维酸性蛋白 (GFAP) 标记物鉴定星形胶质细胞来源的 EV。使用商业 ELISA 测量 S100B 蛋白的水平。使用幼年关节炎疾病活动评分（JADAS27，0-57）评估疾病活动性，并使用视觉模拟量表（VAS，0-10 cm）测量疼痛水平。我们的分析显示，与健康对照组相比，幼年特发性关节炎儿童血浆中星形胶质细胞衍生的 EV 浓度显着更高。此外，JADAS27 分数为 1 或更高的儿童表现出明显更高的 EV 水平。 S100B 蛋白仅在 JIA 组中可检测到。 JIA 儿童中星形胶质细胞来源的 EV 水平升高和 S100B 的存在提供了 BBB 破坏和 CNS 受累的证据，特别是在疾病活动度较高的儿童中。这些发现强调了在幼年特发性关节炎综合管理中考虑中枢神经系统健康的重要性。需要进一步的研究来阐明中枢神经系统参与幼年特发性关节炎背后的机制，并开发针对该疾病的关节和中枢神经系统表现的治疗方法。