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Exploring the faecal miRNA profile in familial Mediterranean fever patients and the role of miR-21-5p in inflammatory pathways associated with FMF pathogenesis
A. Chaaban1, Z. Skaineh2, R. Hammoud3, A. Chebly4, L. Karam5, E. Eldawra6, J.-N. Ibrahim7
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
- Center Jacques Loiselet for Medical Genetics and Genomics (CGGM), Faculty of Medicine, Saint Joseph University of Beirut (USJ), Beirut, Lebanon.
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon.
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon. josenoel.ibrahim@lau.edu.lb
CER20014
2026 Vol.44, N°10
PI 2114, PF 2123
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Received: 07/04/2026
Accepted : 08/10/2026
In Press: 26/10/2026
Published: 26/10/2026
Abstract
OBJECTIVES:
Beyond MEFV mutations, epigenetics seems to play an important role in the manifestation of familial Mediterranean fever (FMF). This study aimed to evaluate the differential expression of selected miRNAs in stool samples from FMF patients, and to investigate the functional role of miR-21-5p in FMF-related inflammatory pathways.
METHODS:
Thirty-four FMF patients, 15 patients with Clostridioides difficile infection (CDI), and 25 healthy controls were enrolled in this study. The faecal levels of 27 miRNAs associated with inflammation, apoptosis, and autophagy were quantified by qRT-PCR. The functional role of miR-21-5p in regulating NF-ĸB and pyrin inflammasome pathways was investigated in LPS-stimulated THP-1 derived macrophages transfected with an anti-mir-21-5p inhibitor via western blot.
RESULTS:
Among the 27 analysed miRNAs, eight were significantly upregulated in FMF patients compared with controls, with miR-21-5p, miR-30e-3p, and miR-148a-3p uniquely elevated in FMF. Downregulation of the anti-inflammatory miR-186-5p and miR-374b-5p was observed particularly in M694V homozygous patients, while let-7d-5p, and miR-148b-3p were associated with higher disease severity. Functional inhibition of miR-21-5p in LPS-stimulated THP-1-derived macrophages reduced NF-ĸB activation and decreased the expression of inflammasome-associated proteins except ASC, consistent with ASC-independent modulation of inflammasome signalling, potentially through direct caspase-1 activation.
CONCLUSIONS:
Our findings highlight the role of miRNAs in intestinal inflammation and their potential as diagnostic and prognostic biomarkers in FMF. Our functional data underscore the regulatory role of miR-21-5p in FMF-related inflammatory pathways and warrant further studies to elucidate its therapeutic potential, particularly in patients refractory to colchicine or as an adjunct to existing treatments.
