# Epigenetic and Inflammatory Signatures in Familial Mediterranean Fever: Implication of miR-204-3p and miR-223-3p in Pyrin-Mediated Immune Regulation

## TL;DR

This study explores how certain microRNAs and proteins are linked to inflammation in Familial Mediterranean Fever, a genetic disease.

## Contribution

The study identifies miR-204-3p and miR-223-3p as potential biomarkers in FMF-related immune regulation.

## Key findings

- FMF patients had significantly lower levels of miR-204-3p, miR-223-3p, and DTX1 compared to controls.
- Pyrin levels were significantly higher in FMF patients, suggesting a role in inflammation.
- CTLA-4 levels correlated positively with pyrin and DTX1, indicating ongoing subclinical inflammation.

## Abstract

Objectives: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEFV mutations, leading to recurrent fever and inflammation. Dysregulation of innate and adaptive immunity, including altered expression of microRNAs and immune regulatory molecules, may contribute to disease heterogeneity. The role of CTLA-4, DTX1, and selected miRNAs in FMF pathogenesis remains unclear. Methods: We conducted a case–control study including 48 pediatric FMF patients and 36 age- and sex-matched healthy controls. Serum miR-204-3p and miR-223-3p levels were assessed via qRT-PCR. Plasma concentrations of pyrin, CTLA-4, and DTX1 were measured using ELISA. Clinical data and MEFV mutation types were analyzed in relation to biomarker levels. Results: There was no statistical significance between the groups in plasma CTLA-4 levels. Serum miR-204-3p, miR-223-3p, and plasma DTX1 levels were found to be significantly lower in FMF patients, while plasma pyrin levels (p < 0.05, in all) were significantly higher. CTLA-4 levels were positively correlated with pyrin and DTX1 levels (r = 0.602; p < 0.001; r = 0.740; p < 0.001, respectively). Conclusions: miR-204-3p and miR-223-3p may be associated with FMF pathogenesis. Increased levels of the pyrin protein, encoded by the MEFV gene, may have an important role in apoptotic and inflammatory signaling pathways. A decrease in DTX1 levels and a positive correlation between DTX1 and CTLA-4 suggest that subclinical inflammation may continue in attack-free periods in FMF patients.