NLRP1 Inflammasome is Associated to IL-18 in Familial Mediterranean Fever and MEFV Variants

Vollständiger Abstract

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Abstract “Familial Mediterranean Fever (FMF) (OMIM #249,100) is the most prevalent hereditary autoinflammatory disease globally, though it remains rare outside Mediterranean populations. FMF is caused by gain-of-function mutations in the MEFV gene, which encodes the immune regulatory protein pyrin. Recent studies suggest that multiple inflammasomes, including the pyrin inflammasome, may work synergistically to enhance their activity. In this study, we focused on NLRP1, and IL-18, an interleukin found at elevated levels in FMF and MEFV variant patients. We observed that silencing or knocking out NLRP1 reduced the inflammatory profile associated with MEFV at the cellular level. NLRP1 inhibition led to decreased release of interleukins, inflammasome-related proteins, and pyroptosis in both patient-derived cells and cultured model systems under proinflammatory conditions. Given that common treatments like colchicine or anakinra can lose effectiveness over time or in certain patients, these findings offer potential avenues for new therapeutic strategies in FMF management.”