Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Pediatr Rheumatol Online J. 2021 Dec 28;19(1):173. doi: 10.1186/s12969-021-00660-9.
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms.
Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA).
The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA.
We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.
本研究旨在对全身型幼年特发性关节炎(sJIA)进行免疫分析,以确定具有临床应用价值的生物标志物,并揭示新的免疫机制。
通过高灵敏度的蛋白质免疫分析,对包括 21 例 sJIA 患者和 60 例年龄和性别匹配的健康对照者在内的临床特征明确的队列的血浆样本进行免疫分析。基于在横断面和配对分析中显著上调或下调的生物标志物,采用 Ingenuity 通路分析(IPA)探索相关的经典通路和细胞功能。
与健康对照者相比,在活动期 sJIA 中,研究证实了 IL6、IL18 和 S100A12 等研究较为充分的 sJIA 生物标志物的升高。与健康对照者相比,仅发现 IL18 在缓解期 sJIA 中升高。在活动期和/或缓解期 sJIA 患者及健康对照者中,发现了包括 CASP8、CCL23、CD6、CXCL1、CXCL11、CXCL5、EIF4EBP1、KITLG、MMP1、OSM、SIRT2、SULT1A1 和 TNFSF11 等新的差异表达因子。根据 IPA 中输入的有限因子,无法预测明显的通路激活。高迁移率族蛋白 B1(HMGB1)是一种与一系列炎症性疾病相关的损伤相关分子模式,在活动期 sJIA 中比缓解期 sJIA 中更高。
我们可以鉴定出一组新的生物标志物,将活动期 sJIA 与缓解期 sJIA 或健康对照者区分开来。我们的发现使我们更好地理解了 sJIA 中活跃的免疫机制,并有助于开发未来的诊断和治疗策略。