Altered miR-193a-5p expression in children with cow's milk allergy

Abstract

Background

Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggest that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls.

Methods

Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed.

Results

Among the miRNAs differently expressed, 2 were up-regulated and 14 were down-regulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most down-regulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted up-regulated in CMA patients compared to healthy controls. Peripheral blood CD4⁺ T cells transfected with a miR193a-5 inhibitor showed a significant up-regulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls.

Conclusions

Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.

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