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Journal Articles Annals of the Rheumatic Diseases Year : 2020

Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor

Sophie Georgin-Lavialle
Mathieu Gerfaud-Valentin
Pascal Sève
Léa Savey
  • Function : Author

Abstract

Background and Objective Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation upon identification of bi-allelic pathogenic MEFV variants. MEFV encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID). Methods Real time pyroptosis and IL-1β secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71), and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by ROC curve analyses. Results Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1β dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by MEFV gene dosage and MEFV mutations in a similar way as clinical phenotypes are. Conclusions UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.

Domains

Immunology
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Dates and versions

hal-02963374 , version 1 (11-06-2021)

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Flora Magnotti, Tiphaine Malsot, Sophie Georgin-Lavialle, Fatima Abbas, Amandine Martin, et al.. Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor. Annals of the Rheumatic Diseases, 2020, pp.annrheumdis-2020-218366. ⟨10.1136/annrheumdis-2020-218366⟩. ⟨hal-02963374⟩
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