Inflammation-related Differentially Expressed Common MiRNAs in Systemic Autoinflammatory Disorders Patients Can Regulate the Clinical Course

Objectives: Systemic autoinflammatory diseases (SAIDs) are caused by the malfunctioning of the innate immune system factors. Clinical heterogeneity and undefined pathobiology are common phenomena among SAIDs. In this study, we aimed to assess the involvement of microRNAs in regulating these complex diseases.

Methods: The expression pattern of different miRNAs was compared between SAID patients with high autoinflammatory disease activity index (AIDAI) score and with low AIDAI score, and their role in inflammation-related pathways was investigated. Differentially expressed miRNAs were determined using the Multi Experiment Viewer (MEV) and Transcriptome Analysis Console (TAC) analysis tools using miRNA microarray. Potential targets of miRNAs were enriched for inflammation-related genes and validated using qRT-PCR analysis.

Results: Upon performing microarray analysis, 40 differentially expressed miRNAs were identified between mild familial Mediterranean fever (FMF) patients and severe SAID patients. Thereafter, 21 of 40 miRNAs were found to be potentially involved in inflammatory pathways, of which, 8 were further validated through qRT-PCR. The targets of these 8 miRNAs (miR-29b-3p, miR-29c-3p, miR-30e-3p, miR-130b-3p, miR-148a-3p, miR-186-5p, miR-197-3p, and miR-374b-5p) belonged to the inflammation-related genes and pathways.

Conclusions: This is the first study to identify miRNAs that might be associated with a more severe disease form of monogenic autoinflammatory diseases. All these miRNAs were associated with cytokine-mediated pathways and might be used for establishing diagnostic and therapeutic methods.