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Differential Cytokine Expression in the Duodenum and Rectum of Children with Non-Immunoglobulin E-Mediated Cow’s Milk Protein Allergy

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Abstract

Background

Cow’s milk protein allergy (CMPA) is the most prevalent food allergy in children, and its pathogenesis remains poorly understood. It has been shown that the combination of genetic predisposition, perinatal factors, and intestinal imbalance of the immune response mediated by cytokines may play an essential role in CMPA pathogenesis.

Aim

To characterize the gene expression of Th1, Th2, and Th17 cytokines in the duodenum and rectum in patients with CMPA.

Methods

This is an observational, descriptive, cross-sectional, prospective study. We used specific IgE (ImmunoCAP®) in serum and biopsies from the rectum and duodenum for the detection of cytokine messenger RNA levels by real-time PCR in patients with a positive oral food challenge for CMPA. We analyzed the relative quantification of the gene expression of cytokines by real-time PCR, and we used the housekeeping gene GAPDH for normalization purposes.

Results

Thirty children (13 male and 17 female) were evaluated. All patients had an open challenge for CMPA. IgE specific to casein, alfa-lactalbumin, and beta-lactoglobulin was negative in all patients. In terms of cytokine levels, the levels of TNFα, IL-6, IL-12 (Th1), IL-4, IL-10, IL-13 (Th2), and IL-17 were found to be higher in the rectum than in the duodenum (p < 0.05). IL-15 was found to be higher in the duodenum than in the rectum (p < 0.05).

Conclusions

In the present study we observed that the immune response in CMPA seems to be mediated by a Th1, Th2, and Th17 cytokine profile, with the rectum being the main affected site.

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Acknowledgments

We thank the Molecular Allergy Laboratory in Mexico City, especially Elizabeth Figueroa for all her support in the collection and processing of Specific IgE samples (Immunocap®).

Funding

This work was supported by funds from the Inflammatory Bowel Disease Clinic at the National Institute of Medical Sciences and Nutrition.

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Authors and Affiliations

  1. Department of Pediatric Gastroenterology and Nutrition, Instituto Nacional de Pediatría, Distrito Federal, Mexico

    Erick M. Toro-Monjaraz, Flora Zárate-Mondragón, Ericka Montijo-Barrios, José Cadena-León, David Avelar-Rodríguez, Jaime Ramírez-Mayans & Roberto Cervantes-Bustamante

  2. Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Vasco de Quiroga #15, Col. Sección XVI, 14000, Mexico City, D.F., Mexico

    Gabriela Fonseca-Camarillo & Jesús K. Yamamoto-Furusho

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  1. Erick M. Toro-Monjaraz
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  2. Gabriela Fonseca-Camarillo
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  3. Flora Zárate-Mondragón
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  8. Roberto Cervantes-Bustamante
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Corresponding author

Correspondence to Jesús K. Yamamoto-Furusho.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The present study was approved by the research and bioethics committee of the National Institute of Pediatrics in Mexico City. We complied with the declaration of Helsinki version 2008. Informed written consent was obtained from all patients’ parents.

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Toro-Monjaraz, E.M., Fonseca-Camarillo, G., Zárate-Mondragón, F. et al. Differential Cytokine Expression in the Duodenum and Rectum of Children with Non-Immunoglobulin E-Mediated Cow’s Milk Protein Allergy. Dig Dis Sci 66, 3769–3775 (2021). https://doi.org/10.1007/s10620-020-06743-z

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  • DOI: https://doi.org/10.1007/s10620-020-06743-z

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