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Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor
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Edité par CCSD ; BMJ Publishing Group -
International audience. 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.ResultsInflammasome 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 genedosage and MEFV mutations in a similar way as clinical phenotypes are.ConclusionsUCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.
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