RT Journal Article SR Electronic T1 Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 1107 OP 1113 DO 10.1136/annrheumdis-2019-215051 VO 78 IS 8 A1 Faekah Gohar A1 Angela McArdle A1 Melissa Jones A1 Niamh Callan A1 Belinda Hernandez A1 Christoph Kessel A1 Maria Miranda-Garcia A1 Miha Lavric A1 Dirk Holzinger A1 Carolin Pretzer A1 Elke Lainka A1 Sebastiaan J Vastert A1 Sytze de Roock A1 Oliver FitzGerald A1 Stephen R Pennington A1 Dirk Foell YR 2019 UL http://ard.bmj.com/content/78/8/1107.abstract AB Objectives The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease. The proposed biphasic model of SJIA also implies a ‘window of opportunity’ to abrogate the development of chronic arthritis. We aimed to identify novel SJIA biomarkers during different disease phases.Methods Children with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA syst ) or polyarticular disease (SJIA poly ). A discovery cohort of n=10 patients per SJIA group, plus n=10 with infection, was subjected to unbiased label-free liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay screens. In a separate verification cohort (SJIA syst , n=45; SJIA poly , n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays.Results Signatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA syst from SJIA poly well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA syst vs SJIA poly ) and 77% (SJIA syst vs infection) of all cases.Conclusions Molecular signatures differentiating two phenotypes of SJIA were identified suggesting shifts in underlying immunological processes in this biphasic disease. Biomarker signatures separating SJIA in its initial autoinflammatory phase from the main differential diagnosis (ie, infection) could aid early-stage diagnostic decisions, while markers of a phenotype switch could inform treat-to-target strategies.