> Detailanzeige

Gohar, Faekah; McArdle, Angela; Jones, Melissa; Callan, Niamh; Hernandez, Belinda; Kessel, Christoph; Miranda-Garcia, Maria; Lavric, Miha; Holzinger, Dirk; Pretzer, Carolin; Lainka, Elke; Vastert, Sebastiaan J; de Roock, Sytze; FitzGerald, Oliver; Pennington, Stephen R; Foell, Dirk

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

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis
  • Beteiligte: Gohar, Faekah; McArdle, Angela; Jones, Melissa; Callan, Niamh; Hernandez, Belinda; Kessel, Christoph; Miranda-Garcia, Maria; Lavric, Miha; Holzinger, Dirk; Pretzer, Carolin; Lainka, Elke; Vastert, Sebastiaan J; de Roock, Sytze; FitzGerald, Oliver; Pennington, Stephen R; Foell, Dirk
  • Erschienen: BMJ, 2019
  • Erschienen in: Annals of the Rheumatic Diseases
  • Sprache: Englisch
  • DOI: 10.1136/annrheumdis-2019-215051
  • ISSN: 0003-4967; 1468-2060
  • Schlagwörter: General Biochemistry, Genetics and Molecular Biology ; Immunology ; Immunology and Allergy ; Rheumatology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Objectives</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Children with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA<jats:italic><jats:sup>syst</jats:sup></jats:italic>) or polyarticular disease (SJIA<jats:italic><jats:sup>poly</jats:sup></jats:italic>). 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<jats:italic><jats:sup>syst</jats:sup></jats:italic>, n=45; SJIA<jats:italic><jats:sup>poly</jats:sup></jats:italic>, n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Signatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA<jats:italic><jats:sup>syst</jats:sup></jats:italic> from SJIA<jats:italic><jats:sup>poly</jats:sup></jats:italic> well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA<jats:italic><jats:sup>syst</jats:sup></jats:italic> vs SJIA<jats:italic><jats:sup>poly</jats:sup></jats:italic>) and 77% (SJIA<jats:italic><jats:sup>syst</jats:sup></jats:italic> vs infection) of all cases.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>