Purpose of review: The gene responsible for familial Mediterranean Fever (FMF), MEditerranean FeVer (MEFV), was identified two decades ago; however, only recent studies have shed light on its pathogenesis. This review focuses on recent studies that have led us to more fully understand FMF pathogenesis.
Recent findings: The vast majority of FMF-associated mutations are located in the B30.2 (SPRY) domain, which functions as a ligand binding or a signal transduction domain, at the carboxy terminus of the protein. As a result, B30.2 mutations may lead to postponed apoptosis and inflammation due to the reduced ability of pyrin to control interleukin-1beta (IL-1beta) activation. Development of AA amyloidosis is rare in FMF patients without amyloidogenic single nucleotide polymorphisms (SNPs) (713T allele) of the SAA1 gene. High macrophage inflammatory protein-1alpha levels during FMF attacks might be responsible for the enhancement of T-cell mediated immunity in FMF. IL-1beta-511 (C/T), IL-1beta+3953 (C/T) and IL-1Ra VNTR polymorphisms were not associated with the development of amyloid in FMF patients.
Summary: Future studies should focus on defining the impact of MEFV and other mutations on the pathological course of FMF, and to understand the exact pathophysiology of those patients who are unresponsive to colchicine, which may help to develop novel therapeutic options for the management and improvement of prognosis.