Abstract
ObjectiveJuvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging.MethodsWe analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later.ResultsTwo-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months.ConclusionOur data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.
Highlights
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders currently classified according to the International League of Associations for Rheumatology (ILAR) which collectively represent the most common rheumatic diseases in childhood [1]
erythrocyte sedimentation rate (ESR) and serum S100A12 were identified as biomarkers for a higher risk of subsequent development of JIA-associated uveitis in the prospective Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA) study [13]
Biomarker analyses Blood samples collected at baseline and at the 3-month follow-up visit were tested for C-reactive protein (CRP), S100A8/A9, and S100A12 as well as ESR
Summary
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders currently classified according to the International League of Associations for Rheumatology (ILAR) which collectively represent the most common rheumatic diseases in childhood [1]. Biomarkers have shown potential as diagnostic and prognostic tools in JIA, as tools for assessment of disease activity and severity, for determination of the likelihood of clinical remission or relapse, and the response to therapy. Assessment of disease activity in JIA usually involves laboratory markers of inflammation already proven in clinical practice such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Several studies have addressed biomarkers in JIA patients so far, and several candidates were identified in exploratory studies, including many different chemokines and cytokines [7, 8]. For most of these biomarkers, validation studies have not yet been performed. ESR and serum S100A12 were identified as biomarkers for a higher risk of subsequent development of JIA-associated uveitis in the prospective Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA) study [13]
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