INSAID

Systemic autoinflammatory diseases (SAID) are highly heterogeneous monogenic or multifactorial conditions whose onset is secondary to deregulation of mechanisms controlling the immune innate response. Molecular analysis is able to provide a definitive diagnosis in some patients with inherited SAID, but the results can be inconclusive or even misleading in several other cases. In daily practice, the number of patients having a clinical picture highly consistent with an autoinflammatory disease, but are orphan of a molecular characterization (undefined SAID) is still high. The main goals of the presented project are: i) to establish consensus among experts on the correct interpretation of genetic tests in accordance with available clinical criteria; ii) To improve the performance of genetic diagnosis; iii) to evaluate the impact of modifier factors in the phenotype of defined SAID, using Familial Mediterranean Fever (FMF) as a prototype; iv) to establish a multidimensional platform for the identification of new genes and conditions for orphan patients. Data and information sharing among the participating groups will be facilitated by establishing a proper common database and by implementing a pilot bioinformatics platform. This project integrates three essential ingredients i) well characterized valuable patient material, ii) a state-of-the-art genomic approaches and iii) innovative functional assays, which all together are making the most promising approach for the identification of causal DNA variants, new genes and biomarkers in genetically orphan patients.