Abstract
Abstract
Background
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.
Methods
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).
Results
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.
Conclusions
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.
Funder
Reumatikerförbundet
Magnus Bergvalls Stiftelse
Ulla och Gustaf af Ugglas Stiftelse
Stiftelsen Samariten
Karolinska Institutet
Vetenskapsrådet
region Stockholm
China Scholarship Council
Karolinska Institute
Publisher
Springer Science and Business Media LLC
Subject
Immunology and Allergy,Rheumatology,Pediatrics, Perinatology and Child Health
Reference40 articles.
1. Lee JJ, Schneider R. Systemic juvenile idiopathic arthritis. Pediatr Clin. 2018;65(4):691–709. https://doi.org/10.1016/j.pcl.2018.04.005.
2. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.
3. Pardeo M, Bracaglia C, De Benedetti F. Systemic juvenile idiopathic arthritis: new insights into pathogenesis and cytokine directed therapies. Best Pract Res Clin Rheumatol. 2017;31(4):505–16. https://doi.org/10.1016/j.berh.2018.02.002.
4. Kessel C, Hedrich CM, Foell D. Innately adaptive or truly autoimmune: is there something unique about systemic juvenile idiopathic arthritis? Arthritis Rheum. 2020;72(2):210–9. https://doi.org/10.1002/art.41107.
5. Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the Interleukin-1 receptor antagonist Anakinra in patients with systemic-onset juvenile idiopathic arthritis (Anajis trial). Ann Rheum Dis. 2011;70(5):747–54. https://doi.org/10.1136/ard.2010.134254.
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