Periodic Reporting for period 1 - FMF-Dia (Immunological Diagnosis of Familial Mediterranean Fever)
Okres sprawozdawczy: 2016-10-01 do 2018-03-31
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide, affecting an estimated 150 thousand patients. The disease is highly prevalent in countries of the Mediterranean basin, the Caucasus and the Middle East, with 1:1000 up to 1:500 inhabitants being affected in countries like Turkey, Israel and Armenia. FMF has further spread to other regions of the world with migrations of these populations in modern history and today. Colchicine therapy is the gold standard for FMF patients, but correct FMF diagnosis is desired before onset of therapy. Diagnosis of FMF is currently based on clinical presentation, and is further supported by review of ethnic origin, family history and genetic analysis of disease-associated MEFV alleles. However, clinical and genetic diagnosis of FMF are complicated by significant overlap of the clinical picture with related autoinflammatory diseases, and over 330 FMF alleles of MEFV have been described. Common genetic tests focus on the most common mutations in exons 2 and 10 of MEFV, but mutations may also occur in other parts of the MEFV gene. Consequently, genetic analysis of FMF is sometimes inconclusive, and correct diagnosis of FMF may sometimes be delayed for years. In the context of this ERC PoC project, we have established and validated an immunological assay that for the first time allows stratification of FMF patients based on the differential immunological response. The availability of a single robust, affordable and convenient assay that immunologically stratifies FMF patients from FMF-like and other autoinflammatory disease patients will be instrumental for improving timely and correct identification of FMF patients for colchicine therapy, and (where desired) will enable more cost-effective selection of patients for more extensive genetic testing. In the context of our PoC studies, we have optimized and standardized the experimental variables of the assay parameters, and analyzed the whole blood, monocyte, granulocyte and PBMC inflammasome response of a cohort of 57 clinically diagnosed FMF and 48 control individuals from different European clinical centers to establish proof-of-concept that the assay reliably and selectively identifies FMF patients. We also included a cohort of 6 HIDS and 4 PAPA patients to demonstrate that only FMF patients are identified by the testing procedure.Although diagnostic companies that have been approached recognized the societal and clinical value of such FMF diagnostic test, the market size was deemed too limited to justify the investment that would be needed for successful commercialization.