V D'Argenio1,2, V Del Monaco1, L Paparo3, F D E De Palma1, R Nocerino3, F D'Alessio1, F Visconte1,2, V Discepolo1,3, L Del Vecchio1,2, F Salvatore1,2,4, R Berni Canani1,3,5. 1. CEINGE-Biotecnologie Avanzate s.c.ar.l., Naples, Italy. 2. Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy. 3. Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. 4. IRCCS-Fondazione SDN, Naples, Italy. 5. European Laboratory for the Investigation of Food-Induced Diseases, University of Naples Federico II, Naples, Italy.
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 have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests 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 upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation 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.
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 have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests 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 upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation 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.
Authors: Bilal Alashkar Alhamwe; Laura A P M Meulenbroek; Désirée H Veening-Griffioen; Tjalling M D Wehkamp; Fahd Alhamdan; Sarah Miethe; Hani Harb; Astrid Hogenkamp; Léon M J Knippels; Elke Pogge von Strandmann; Harald Renz; Johan Garssen; Betty C A M van Esch; Holger Garn; Daniel P Potaczek; Machteld M Tiemessen Journal: Nutrients Date: 2020-10-19 Impact factor: 5.717