Annals of the rheumatic diseases · 2020
Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Magnotti Flora, Malsot Tiphaine, Georgin-Lavialle Sophie, Abbas Fatima, Martin Amandine, Belot Alexandre, Fauter Maxime, Rabilloud Muriel, Gerfaud-Valentin Mathieu, Sève Pascal, Duquesne Agnes, Hot Arnaud, Durupt Stephane, Savey Léa, Giurgea Irina, Grateau Gilles, Henry Thomas, Jamilloux Yvan
Аннотация
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 on identification of biallelic 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 receiver operating characteristic 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.
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 receiver operating characteristic 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.
Предметные рубрики MeSH
AdolescentAdultAgedAged, 80 and overArthritis, JuvenileBehcet SyndromeCase-Control StudiesChildChild, PreschoolCryopyrin-Associated Periodic SyndromesFamilial Mediterranean FeverFemaleFeverFever of Unknown OriginHereditary Autoinflammatory DiseasesHumansImmunologic TestsInflammasomesInterleukin-1betaLupus Erythematosus, SystemicMaleMevalonate Kinase DeficiencyMiddle AgedMonocytesProtein Kinase InhibitorsPyrinPyroptosisSensitivity and SpecificitySepsisStaurosporineStill's Disease, Adult-OnsetYoung Adult