Analysis of microRNAs in familial Mediterranean fever

<div><p>Objectives</p><p>Although Familial Mediterranean fever (FMF) is categorized as autosomal recessive, frequent exceptions to this model exist and therefore we aimed to search epigenetic modifications in this disease.</p><p>Methods</p><p>Ten M694V homozygous FMF patients (the most severe phenotype) were recruited for this study. Patients with inflammatory flare were excluded. Total RNA was extracted from peripheral blood, and microRNA expression profiled using NanoString nCounter technology. These patients were compared to 10 healthy age- and sex-matched controls.</p><p>Results</p><p>Seven hundred nighty-eight mature human miRNAs were probed, 103 of which had expression levels above the negative control probes. Seven miRNAs showed significant differences in expression in samples from FMF patients compared to healthy controls: four miRNAs were upregulated (miR-144-3p, miR-21−5p, miR−4454, and miR-451a), and three were downregulated (miR-107, let−7d−5p, and miR-148b-3p).</p><p>Conclusion</p><p>In this pilot study, we identified epigenetic modifications in clinically quiescent FMF patients. More studies are required for exploration of their contribution to FMF pathogenesis and their potential role as clinical biomarkers.</p></div

Significant differentially expressed miRNAs.

<p>miRNA dispersion analysis demonstrated equal distribution of up- and down-regulated miR transcripts. In FMF patient samples, three miRNAs were downregulated compared to healthy control samples (miR-107, let−7d−5p, and miR-148b-3p), and four miRNAs were upregulated (miR-144-3p, miR-21−5p, miR−4454 and miR-451a).</p

Differentially expressed miRNAs in PBMC from patients with FMF vs. healthy controls and their reported role in immunity.

<p>Differentially expressed miRNAs in PBMC from patients with FMF vs. healthy controls and their reported role in immunity.</p

PCA analysis of miRNAs.

<p>(A) PCA analysis of 103 miRNAs with reasonable expression levels demonstrated a clear separation between the FMF and control groups. (B) PCA analysis of 7 differentially expressed miRNAs revealed distinguishable profiles of the FMF and control groups.</p

Additional file 1: of Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy

Table S1 Definition of adapted ACR JIA response. Table S2 Genes with ≥3-fold differential expression between patients with SJIA and healthy controls, prior to canakinumab treatment. Table S3 List of independent ethics committees or institutional review boards (trial 1). Table S4 List of independent ethics committees or institutional review boards (trial 2). (DOCX 53 kb