Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort
Kristiina Aalto,
Christoph Kessel,
Dirk Foell,
Anders Fasth,
Troels Herlin,
Marite Rygg,
LILLEMOR BERNTSON,
Ellen Nordal,
Mia Glerup,
Ellen Dalen Arnstad,
Veronika Rypdal,
Charlotte Myrup,
Suvi Peltoniemi,
Susanne Schleifenbaum,
Malene Noer Høllsberg,
Anders Ellern Bilgrau
Affiliations
Kristiina Aalto
Paediatric Research Centre, University of Helsinki, Helsinki, Finland
Christoph Kessel
Department of Paediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany
Dirk Foell
Department of Paediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany
Anders Fasth
Department of Paediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Troels Herlin
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Marite Rygg
Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway
LILLEMOR BERNTSON
Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
Ellen Nordal
Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway
Mia Glerup
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Ellen Dalen Arnstad
Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway
Veronika Rypdal
Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway
Charlotte Myrup
Department of Paediatrics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Suvi Peltoniemi
Clinic of Rheumatology, Helsinki University Hospital, Helsinki, Finland
Susanne Schleifenbaum
Department of Paediatric Rheumatology and Immunology, University Hospital Münster, Münster, Germany
Malene Noer Høllsberg
Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Anders Ellern Bilgrau
Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark
Objectives To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting.Methods Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables.Results Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1β (IL-1β), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset.Conclusion Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.
