Abstract
BackgroundThis 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.MethodsImmunoprofiling 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).ResultsThe 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.ConclusionsWe 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.
Highlights
This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis in order to define biomarkers of clinical use as well as reveal new immune mechanisms
Inflammation-associated proteins separate active systemic juvenile idiopathic arthritis (sJIA), inactive sJIA and healthy controls Based on the 69 proteins included in the analysis, the groups of active sJIA, inactive sJIA and healthy controls could be identified but not completely separated by Hierarchical Clustering Analysis (HCA) (Supplementary Fig. S4)
Principal Component Analysis (PCA) showed an overlap, with the active sJIA group more separated by principal components 1 and 2 (PC1 and PC2) from the inactive sJIA group and the healthy control group (Fig. 1A)
Summary
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. Systemic juvenile idiopathic arthritis (sJIA) accounts for 4–17% of juvenile idiopathic arthritis (JIA) cases. It is distinguished from the other JIA subtypes by its clinical features, pathogenetic mechanisms and by treatment. IL18 has been suggested to predict disease activity, to estimate disease severity and development of MAS [8]. Soluble CD163 and IL2 are suggested to detect subclinical MAS and to predict the development of overt MAS in sJIA [11]. Matrix Metalloproteinase 3 (MMP3) have been reported to correlate with the progression of structural joint damage in sJIA [12]
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