Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.
Ann Rheum Dis
; 80(1): 128-132, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33037005
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 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-1ß 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-1ß 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Febre Familiar do Mediterrâneo
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Monócitos
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Estaurosporina
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Inibidores de Proteínas Quinases
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Interleucina-1beta
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Inflamassomos
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Piroptose
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Pirina
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Aged80
Idioma:
En
Revista:
Ann Rheum Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França