Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity

Background: Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow’s milk protein are increasingly considered for therapy and prevention of cow’s milk allergy. The aim of this study was...

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Main Authors: Raphaela Freidl, Victoria Garib, Birgit Linhart, Elisabeth M. Haberl, Isabelle Mader, Zsolt Szépfalusi, Klara Schmidthaler, Nikos Douladiris, Alexander Pampura, Evgeniy Varlamov, Tatiana Lepeshkova, Evgeny Beltyukov, Veronika Naumova, Styliani Taka, Dina Nosova, Olga Guliashko, Michael Kundi, Alina Kiyamova, Stefani Katsamaki, Rudolf Valenta
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/1/111
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author Raphaela Freidl
Victoria Garib
Birgit Linhart
Elisabeth M. Haberl
Isabelle Mader
Zsolt Szépfalusi
Klara Schmidthaler
Nikos Douladiris
Alexander Pampura
Evgeniy Varlamov
Tatiana Lepeshkova
Evgeny Beltyukov
Veronika Naumova
Styliani Taka
Dina Nosova
Olga Guliashko
Michael Kundi
Alina Kiyamova
Stefani Katsamaki
Rudolf Valenta
author_facet Raphaela Freidl
Victoria Garib
Birgit Linhart
Elisabeth M. Haberl
Isabelle Mader
Zsolt Szépfalusi
Klara Schmidthaler
Nikos Douladiris
Alexander Pampura
Evgeniy Varlamov
Tatiana Lepeshkova
Evgeny Beltyukov
Veronika Naumova
Styliani Taka
Dina Nosova
Olga Guliashko
Michael Kundi
Alina Kiyamova
Stefani Katsamaki
Rudolf Valenta
author_sort Raphaela Freidl
collection DOAJ
description Background: Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow’s milk protein are increasingly considered for therapy and prevention of cow’s milk allergy. The aim of this study was to investigate the allergenic activity and ability to induce T cell and cytokine responses of an infant formula based on extensively hydrolyzed cow’s milk protein (whey) (eHF, extensively hydrolyzed formula) supplemented with Galactooligosaccharides (GOS) and <i>Limosilactobacillus fermentum</i> CECT5716 (LF) to determine its suitability for treatment and prevention of CMA. Methods: eHF and standard protein formula based on intact cow’s milk proteins (iPF) with or without Galactooligosaccharide (GOS) and <i>Limosilactobacillus fermentum</i> CECT5716 (LF) were investigated with allergen-specific antibodies and tested for IgE reactivity and allergenic activity in basophil degranulation assays with sera from cow’s milk (CM)-allergic infants/children. Their ability to stimulate T cell proliferation and cytokine secretion in cultured peripheral blood mononuclear cells (PBMC) from CM-allergic infants and children was studied with a FACS-based carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and xMAP Luminex fluorescent bead-based technology, respectively. Results: An eHF supplemented with GOS and LF exhibiting almost no IgE reactivity and allergenic activity was identified. This eHF induced significantly lower inflammatory cytokine secretion as compared to an intact protein-based infant formula but retained T cell reactivity. Conclusions: Due to strongly reduced allergenic activity and induction of inflammatory cytokine secretion but retained T cell reactivity, the identified eHF may be used for treatment and prevention of CMA by induction of specific T cell tolerance.
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spelling doaj.art-5e7cafb124d54894874c0b90da3f31a22023-12-02T00:46:00ZengMDPI AGNutrients2072-66432022-12-0115111110.3390/nu15010111Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell ReactivityRaphaela Freidl0Victoria Garib1Birgit Linhart2Elisabeth M. Haberl3Isabelle Mader4Zsolt Szépfalusi5Klara Schmidthaler6Nikos Douladiris7Alexander Pampura8Evgeniy Varlamov9Tatiana Lepeshkova10Evgeny Beltyukov11Veronika Naumova12Styliani Taka13Dina Nosova14Olga Guliashko15Michael Kundi16Alina Kiyamova17Stefani Katsamaki18Rudolf Valenta19Center for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, A-1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, A-1090 Vienna, AustriaCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, A-1090 Vienna, AustriaHiPP GmbH & Co. Vertrieb KG, 85276 Pfaffenhofen, GermanyHiPP GmbH & Co. Vertrieb KG, 85276 Pfaffenhofen, GermanyDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergy and Endocrinology, Comprehensive Center of Pediatrics, Medical University Vienna, A-1090 Vienna, AustriaDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergy and Endocrinology, Comprehensive Center of Pediatrics, Medical University Vienna, A-1090 Vienna, AustriaAllergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Allergology and Clinical Immunology, Research and Clinical Institute for Pediatrics Named after Yuri Veltischev at the Pirogov Russian National Research Medical University of the Russian Ministry of Health, 117997 Moscow, RussiaDepartment of Allergology and Clinical Immunology, Research and Clinical Institute for Pediatrics Named after Yuri Veltischev at the Pirogov Russian National Research Medical University of the Russian Ministry of Health, 117997 Moscow, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620014 Ekaterinburg, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620014 Ekaterinburg, RussiaDepartment of Faculty Therapy, Endocrinology, Allergology and Immunology, Ural State Medical University, 620014 Ekaterinburg, RussiaAllergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, 11527 Athens, GreeceAllergy Department, UNIMED Laboratories, 119049 Moscow, RussiaAllergy Department, UNIMED Laboratories, 119049 Moscow, RussiaDepartment for Environmental Heath, Center for Public Health, Medical University of Vienna, A-1090 Vienna, AustriaInternational Center of Molecular Allergology, Ministry of Innovation Development, Tashkent 100174, UzbekistanInternational Center of Molecular Allergology, Ministry of Innovation Development, Tashkent 100174, UzbekistanCenter for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, A-1090 Vienna, AustriaBackground: Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow’s milk protein are increasingly considered for therapy and prevention of cow’s milk allergy. The aim of this study was to investigate the allergenic activity and ability to induce T cell and cytokine responses of an infant formula based on extensively hydrolyzed cow’s milk protein (whey) (eHF, extensively hydrolyzed formula) supplemented with Galactooligosaccharides (GOS) and <i>Limosilactobacillus fermentum</i> CECT5716 (LF) to determine its suitability for treatment and prevention of CMA. Methods: eHF and standard protein formula based on intact cow’s milk proteins (iPF) with or without Galactooligosaccharide (GOS) and <i>Limosilactobacillus fermentum</i> CECT5716 (LF) were investigated with allergen-specific antibodies and tested for IgE reactivity and allergenic activity in basophil degranulation assays with sera from cow’s milk (CM)-allergic infants/children. Their ability to stimulate T cell proliferation and cytokine secretion in cultured peripheral blood mononuclear cells (PBMC) from CM-allergic infants and children was studied with a FACS-based carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and xMAP Luminex fluorescent bead-based technology, respectively. Results: An eHF supplemented with GOS and LF exhibiting almost no IgE reactivity and allergenic activity was identified. This eHF induced significantly lower inflammatory cytokine secretion as compared to an intact protein-based infant formula but retained T cell reactivity. Conclusions: Due to strongly reduced allergenic activity and induction of inflammatory cytokine secretion but retained T cell reactivity, the identified eHF may be used for treatment and prevention of CMA by induction of specific T cell tolerance.https://www.mdpi.com/2072-6643/15/1/111allergycow’s milk allergyallergenhypoallergenic infant formula
spellingShingle Raphaela Freidl
Victoria Garib
Birgit Linhart
Elisabeth M. Haberl
Isabelle Mader
Zsolt Szépfalusi
Klara Schmidthaler
Nikos Douladiris
Alexander Pampura
Evgeniy Varlamov
Tatiana Lepeshkova
Evgeny Beltyukov
Veronika Naumova
Styliani Taka
Dina Nosova
Olga Guliashko
Michael Kundi
Alina Kiyamova
Stefani Katsamaki
Rudolf Valenta
Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
Nutrients
allergy
cow’s milk allergy
allergen
hypoallergenic infant formula
title Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
title_full Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
title_fullStr Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
title_full_unstemmed Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
title_short Extensively Hydrolyzed Hypoallergenic Infant Formula with Retained T Cell Reactivity
title_sort extensively hydrolyzed hypoallergenic infant formula with retained t cell reactivity
topic allergy
cow’s milk allergy
allergen
hypoallergenic infant formula
url https://www.mdpi.com/2072-6643/15/1/111
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