Wen Xingzhao, Aulin Cecilia, Sundberg Erik, Qu Heshuang, Struglics André, Merritt Anne-Sophie, Melén Erik, Altman Maria, Harris Helena Erlandsson
Center for Molecular Medicine, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Unit of Pediatric Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Front Immunol. 2025 Aug 7;16:1599747. doi: 10.3389/fimmu.2025.1599747. eCollection 2025.
We set out to profile the immune mechanisms active in treatment-naïve oligoarticular JIA (oJIA) to improve the knowledge of its immunopathogenesis, to identify potential biomarkers that can aid diagnosis, predictions and that correlate with clinical disease parameters.
Using Olink proteomics (inflammation panel measuring 92 markers), we defined and compared the inflammation profiles of 38 plasma and 62 synovial fluid (SF) oJIA samples, 38 plasma samples from healthy age- and sex-matched controls (HC), 12 SF samples from non-arthritic controls and 26 SF samples from knee injury patients. Clinical data for the oJIA cohort were retrieved from the Swedish pediatric rheumatology quality register and medical charts.
Plasma inflammation profiles of oJIA and HC were largely overlapping, with IL6 and MMP-1 significantly upregulated in oJIA. In SF, 48 differentially expressed proteins (DEPs) were identified in oJIA, highlighting immune pathways like leukocyte migration, cell chemotaxis and adaptive immunity. Comparative analysis revealed 13 proteins specific to oJIA. Correlations were found between DEPs in oJIA SF and clinical parameters (cJADAS-71, pain, health impact score). In plasma, IL6 and MMP-1 showed strong correlation with disease activity and pain, respectively. CXCL9, CXCL10 and CXCL11 were identified as potential predictive biomarkers for disease progression.
The overlap in plasma inflammation profiles of oJIA and HCs suggests local rather than systemic inflammation in oJIA and underlines the need to study oJIA immunopathogenesis using SF samples. The oJIA SF inflammation profiles indicative of adaptive immune reactions separated oJIA from knee-injury patients and can be exploited for diagnostic purposes. Increased SF levels of CXCL9, CXCL10 and CXCL11 were associated with chronic disease progression and could serve as prognostic biomarkers and early treatment targets.
我们着手剖析初治寡关节型幼年特发性关节炎（oJIA）中活跃的免疫机制，以增进对其免疫发病机制的了解，识别有助于诊断、预测且与临床疾病参数相关的潜在生物标志物。
使用欧林克蛋白质组学技术（炎症检测板可检测92种标志物），我们定义并比较了38份血浆和62份滑膜液（SF）oJIA样本、38份来自年龄和性别匹配的健康对照（HC）的血浆样本、12份来自非关节炎对照的SF样本以及26份来自膝关节损伤患者的SF样本的炎症谱。oJIA队列的临床数据从瑞典儿科风湿病质量登记处和病历中获取。
oJIA和HC的血浆炎症谱有很大重叠，oJIA中IL6和MMP - 1显著上调。在SF中，oJIA中鉴定出48种差异表达蛋白（DEP），突出了白细胞迁移、细胞趋化和适应性免疫等免疫途径。比较分析揭示了13种oJIA特有的蛋白。在oJIA SF中的DEP与临床参数（cJADAS - 71、疼痛、健康影响评分）之间发现了相关性。在血浆中，IL6和MMP - 1分别与疾病活动和疼痛显示出强相关性。CXCL9、CXCL10和CXCL11被确定为疾病进展的潜在预测生物标志物。
oJIA和HC的血浆炎症谱重叠表明oJIA存在局部而非全身性炎症，并强调了使用SF样本研究oJIA免疫发病机制的必要性。oJIA SF炎症谱表明适应性免疫反应将oJIA与膝关节损伤患者区分开来，可用于诊断目的。SF中CXCL9、CXCL10和CXCL11水平升高与慢性病进展相关，可作为预后生物标志物和早期治疗靶点。
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