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

Authors:
Faekah Gohar
Faekah Gohar
Interdisciplinary Centre for Clinical Research IZKF
Melissa Jones
Melissa Jones
University of North Carolina at Charlotte
Niamh Callan
Niamh Callan
UCD Conway Institute of Biomolecular and Biomedical Research
Belinda Hernandez
Belinda Hernandez
University College Dublin
Ireland
Christoph Kessel
Christoph Kessel
University Children's Hospital
Sweden
Maria Miranda-Garcia
Maria Miranda-Garcia
University of Münster

Ann Rheum Dis 2019 Apr 20. Epub 2019 Apr 20.

Department of Paediatric Rheumatology and Immunology, University of Münster, Münster, Germany

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 ) or polyarticular disease (SJIA ). 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 , n=45; SJIA , 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 from SJIA well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA vs SJIA ) and 77% (SJIA 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.

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Source
http://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2019-21505
Publisher Site
http://dx.doi.org/10.1136/annrheumdis-2019-215051DOI Listing
April 2019
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