幼年特发性关节炎患儿的血脑屏障通透性与星形胶质细胞衍生的细胞外囊泡：一项横断面研究

Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis: a cross-sectional study.

作者信息

Berntson Lillemor, Elfving Andreas, Samuelsson Alice Gabrielsson, Öman Anders, Mobarrez Fariborz

机构信息

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.

出版信息

Pediatr Rheumatol Online J. 2024 Apr 26;22(1):47. doi: 10.1186/s12969-024-00984-2.

DOI:10.1186/s12969-024-00984-2

PMID:38671467

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11046815/

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSION

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.

摘要

背景

幼年特发性关节炎（JIA）是儿童中最常见的风湿性疾病，其炎症过程得到了广泛研究，主要特征是对关节健康的影响。新出现的证据表明，JIA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衍生的细胞外囊泡（EVs）和S100B蛋白的存在情况，来调查JIA中潜在的中枢神经系统受累情况，这两者均指示星形胶质细胞活性和血脑屏障（BBB）完整性。

方法

对90名诊断为JIA的儿童和10名年龄和性别匹配的健康对照者的乙二胺四乙酸（EDTA）血浆进行流式细胞术测量，分析细胞外囊泡。使用针对水通道蛋白4（AQP - 4）和胶质纤维酸性蛋白（GFAP）的标记物通过流式细胞术鉴定星形胶质细胞衍生的EVs。使用商业酶联免疫吸附测定（ELISA）测量S100B蛋白水平。使用幼年关节炎疾病活动评分（JADAS27，0 - 57）评估疾病活动度，并使用视觉模拟量表（VAS，0 - 10厘米）测量疼痛水平。

结果

我们的分析显示，与健康对照相比，JIA患儿血浆中星形胶质细胞衍生的EVs浓度显著更高。此外，JADAS27评分≥1的儿童这些EVs水平明显更高。S100B蛋白仅在JIA组中可检测到。

结论

JIA患儿中星形胶质细胞衍生的EVs水平升高以及S100B的存在提供了血脑屏障破坏和中枢神经系统受累的证据，特别是在疾病活动度较高的患儿中。这些发现强调了在JIA综合管理中考虑中枢神经系统健康的重要性。需要进一步研究以阐明JIA中枢神经系统受累背后的机制，并开发针对该疾病关节和中枢神经系统表现的治疗方法。