Epigenetic regulators and inflammation antagonists in familial Mediterranean fever: the role of hsa-miR-335-5p, hsa-miR-26b-5p, hsa-miR-16-5p miRNAs and IL-36Ra levels in pathogenesis

Abstract

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by mutations in the MEFV and an over-activation of the pyrin inflammatory cascade. In this study, the roles of three specific microRNAs (miRNAs) and the inflammatory cytokine antagonist IL-36Ra in the pathogenesis of FMF were investigated due to their potential roles in chronic inflammation. 40 FMF patients and 45 healthy control individuals who applied to the Balikesir University Genetic Disorders Evaluation Center between February 2021 and June 2024 were included in the study. miRNA expression levels were determined by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and IL-36Ra protein levels were determined using the ELISA method. Gene expression levels were analyzed by the 2–ΔΔCt method. A significant decrease (p<0.005) in hsa-miR-335-5p and hsa-miR-26b-5p expression levels and a significant increase (p<0.005) in hsamiR-16-5p and IL-36Ra protein levels were observed in FMF patients. These findings point to the existence of a two-way molecular mechanism in FMF pathogenesis: on one hand, there is a deficit in epigenetic regulators with anti-inflammatory properties, such as hsa-miR-335-5p and hsa-miR-26b-5p, while on the other hand, molecules like hsa-miR-16-5p and IL36Ra increase as a compensatory response to balance the inflammatory load. These molecules show promise as potential biomarkers for the diagnosis and follow-up of FMF.