miR-21 and cathepsin B in familial Mediterranean fever: novel findings regarding their impact on disease severity.

Abstract

Objective: The limited predictive effect of genotype on familial Mediterranean fever (FMF) phenotype suggests that epigenetic factors and alternative mechanisms that may cause IL-1β release could contribute to phenotypic heterogeneity. The objective of this study was to examine the role of IL-1β levels and miR-21-5p, cathepsin B and pyrin levels, which were identified as potential factors causing IL-1β release through the use of bioinformatics tools, in the pathogenesis of FMF and their relationship with disease severity.

Materials and methods: 50 paediatric patients with FMF and 40 healthy children were enrolled in this study. Patients were divided into subgroups according to Pras disease severity score. Serum miR-21-5p expression levels were assessed by qRT-PCR, while serum pyrin, IL-1β and cathepsin B levels were determined by ELISA.

Results: Serum miR-21-5p was significantly downregulated in FMF patients compared with the control group (p<0.001), while serum pyrin, IL-1β and cathepsin B levels were markedly elevated (p<0.001 for each). Only miR-21-5p was negatively correlated with IL-1β (r=-0.855; p<0.001). In moderately severe FMF patients, miR-21-5p exhibited a statistically significant downregulation (p<0.001), whereas IL-1β and cathepsin B showed a statistically significant increase (p<0.001 and p<0.05, respectively). Furthermore, the Pras score showed a strong negative correlation (r=-0.738; p<0.001) with miR-21-5p levels. Multivariate logistic regression showed that in FMF, a one-unit decrease in miR-21 increased disease severity risk 6.76-fold, while a one-unit increase in cathepsin B raised it 1.71-fold.

Conclusion: This might be considered one of the mechanisms for subclinical inflammation in paediatric FMF patients through increased activation of cytokines via the downregulation of miR-21-5p. Our findings suggest that miR-21-5p and IL-1β play key roles in subclinical inflammation, and these molecules might be a potential therapeutic target.