Characterization of a Functional Test for Mediterranean Family Fever Screening - 2

Study Overview
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Brief Summary
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Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease (prevalence: 1-5 / 10,000 inhabitants). It is caused by mutations in the MEFV gene, which encodes variants of the Pyrine inflammasome. Inflammasomes are protein complexes of the innate immunity that produce pro-inflammatory cytokines (interleukin-1β). In vitro, our preliminary results demonstrated that the activation of the inflammatory pyrine (measured by the concentration of interleukin-1β) by kinase inhibitors is significantly increased in FMF patients compared to healthy subjects. Furthermore, a measurement of cell death gave significant results in differentiating the patients from the controls. The performance of this functional has been tested, fast and simple diagnostic test on common mutations and wish to assess its characteristics for MEFV mutations. The investigators hypothesize that this quick and simple functional test can serve as a diagnostic tool for FMF and can quantitatively discriminate against patients with different mutations (genotypes).

Official Title
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Characterization of a Functional Test for Mediterranean Family Fever Screening - 2

Conditions
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Familial Mediterranean Fever, MEFV Gene Mutation

Intervention / Treatment
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* Biological: one additional blood sample during a planned blood test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 4 years of age or older or adults Having a clinical picture compatible with an FMF and a previous genetic analysis finding at least one mutation of the MEFV gene pathogenic or possibly pathogenic for the FMF group; Newly diagnosed or in the process of follow-up (with no time limit or evolutionary criteria); During specific or non-specific treatment of the disease or without treatment; For whom a blood test is planned as part of routine care; Whose informed non-opposition has been collected (or parental non-opposition in the case of a minor patient); Exclusion Criteria: Person under legal protection or under the protection of justice or any other protective measures; Person out of state to express their consent; Person in emergency situation, vital or not; Known infections with HIV and / or HBV and / or HCV;

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children or adult with Familial Mediterranean fever<br>Considering 5 clearly pathogenic (homozygous) genotypes, 15 possibly pathogenic genotypes (5 pathogenic mutations in the heterozygous state, 10 possibly pathogenic mutations in the homozygous or heterozygous state), a number of 80 patients will be necessary to cover the correlation analysis genotype / phenotype. The study does not change the usual course of care. Only an additional blood sample (4 ml for children under 12 and 10 ml for children 12 and over and adults) during a planned blood test is specific to research (no risk added). The benefit / risk balance therefore remains unchanged with regard to the usual care of patients. | Biological: one additional blood sample during a planned blood test<br>* The study does not change the usual course of care. Only an additional blood sample (4 ml for children under 12 and 10 ml for children 12 and over and adults) during a planned blood test is specific to research (no risk added). The benefit / risk balance therefore remains unchanged with regard to the usual care of patients.<br>|
| Healthy blood donor<br>Healthy blood donor | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of interleukin-1β | quantification of the capacity of the concentration of interleukin-1β measured in the supernatants of primary monocytes in response to kinase inhibitors, to discriminate between FMF subjects among themselves according to genotypes, and among control subjects (healthy subjects). All samples will be analysed in the INSERM Unit 1111 - CIRI Centre International de Recherche en Infectiologie - Lyon - Team Inflammasome, bacterial infections and autoinflammation. | At inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Mediterranean fever, Interleukin-1β, MEFV gene mutation, innate immunity