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Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis.

Abstract：

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.

journal_name

Ann Rheum Dis

journal_title

Annals of the rheumatic diseases

authors

Gohar F,McArdle A,Jones M,Callan N,Hernandez B,Kessel C,Miranda-Garcia M,Lavric M,Holzinger D,Pretzer C,Lainka E,Vastert SJ,de Roock S,FitzGerald O,Pennington SR,Foell D

doi

10.1136/annrheumdis-2019-215051

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

1107-1113

issue

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2019-215051

journal_volume

pub_type

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Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis.