Increased Frequency of CTLA-4 and PD-1 Expressing Regulatory T Cells and Basophils With an Activating Profile in Infants With Moderate-to-Severe Atopic Dermatitis Hypersensitized to Food Allergens

Agurtzane Bilbao,Francisco Borrego,Raquel Pérez-Garay,Alex Irurzun,Ane Orrantia,Idoia Rius,Iñigo Terrén,Olatz Zenarruzabeitia,Gabirel Astarloa-Pando

doi:10.3389/fped.2021.734645

Agurtzane Bilbao, Francisco Borrego + Show 7 more

Open Access

https://doi.org/10.3389/fped.2021.734645

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Abstract

Background: Infants with severe atopic dermatitis (AD) may be sensitized to foods that have not been introduced into their diet, posing a risk for developing an immediate hypersensitivity reaction on the first exposure to the food to which they are sensitized. The aim of this work was to perform an analysis of the sensitization profile in infants with moderate-to-severe AD and to identify cellular and molecular markers for food allergy (FA).Methods: Blood samples from healthy donors and children with moderate-to-severe AD were studied. Specific IgE to several allergens were determined using ImmunoCAP FEIA system and ISAC technology. Furthermore, using flow cytometry-based studies, basophils and regulatory T (Treg) cells were phenotypically characterized.Results: 90% of children with AD were sensitized to food antigens before introducing them into the diet, and 100% developed FA. Phenotypic analysis showed a significantly higher percentage of CTLA-4 and PD-1 expressing Treg cells in AD patients than in healthy controls. Basophils from patients exhibited a marked reduction in the expression of CD300a, higher expression of FcεRI and CXCR4, and to some extent higher expression of CD63 and CD300c.Conclusions: Infants with moderate-to-severe AD are at high risk of being sensitized to food allergens. Therefore, to avoid allergic reactions, broad-spectrum sensitization studies are necessary before introducing complementary diet. Increased expression of CTLA-4 and PD-1 suggests greater suppressive potential of Treg cells in infants with AD than healthy controls. Furthermore, our results suggest a role for CD300 molecules on circulating basophils as possible biomarkers for FA susceptibility.

Highlights

Atopic dermatitis (AD) is a common inflammatory skin disease of increasing prevalence that affects 7–14% of adults and 10– 20% of children globally [1]
There are studies showing that the early introduction of solid food at 4– 6 months of age reduces the risk of developing food allergy (FA) in patients with severe AD not yet sensitized [12,13,14], which is changing the pattern of complementary feeding in children with AD
The inclusion criterion was a diagnosis of AD in the first 6 months of life, either for lesions on the face and/or large areas that had required topical corticosteroids for more than 7 days a month or generalized lesions that had been treated with a course of systemic corticosteroids

Summary

Introduction

Atopic dermatitis (AD) is a common inflammatory skin disease of increasing prevalence that affects 7–14% of adults and 10– 20% of children globally [1]. There are studies showing that the early introduction of solid food at 4– 6 months of age reduces the risk of developing FA in patients with severe AD not yet sensitized [12,13,14], which is changing the pattern of complementary feeding in children with AD. Despite these studies, in the everyday practice of hospitals in our geographic area only milk and egg specific immunoglobulin E (sIgE) are determined in infants with AD. The aim of this work was to perform an analysis of the sensitization profile in infants with moderate-to-severe AD and to identify cellular and molecular markers for food allergy (FA)

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