A Cianferoni1,2, R Saltzman1,2, F Saretta3, S Barni4, E Dudek1, M Kelleher1, J M Spergel1,2. 1. Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 2. Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Ospedale Palmanova, Palmanova, Udine, Italy. 4. Az Ospedaliera A Meyer, Florence, Italy.
Abstract
BACKGROUND: Cow milk (CM) allergy (CMA) affects up to 3% of the paediatric population and recent data suggest that only about 50% will outgrow by age 8. Oral immunotherapy (OIT) is a type of immune-modulating treatment that is able to induce desensitization to food allergens, to increase tolerance threshold, to reduce the risk of anaphylaxis, and to improve the patient's quality of life. The examination of the immunological changes observed during the establishment of food allergy (FA) desensitization in FA patients is a window into the pathogenesis of food allergy and food tolerance development. In this pathway, we have previously found that invariant natural killer T cells (iNKTs) are involved in CM allergy sensitization and now examine their role in OIT. METHODS: In this study, 10 of the 11 children with CM induced anaphylaxis enrolled in a CMA OIT clinical trial and completed the protocol. Peripheral blood iNKTs were quantitatively and qualitatively via flow cytometry characterized ex vivo and after culture with milk lipids before and after completing the OIT protocol. RESULTS: After completing OIT for CM, children were able to reintroduce CM in their diet. For the first time, we demonstrated that OIT induced a significant increase in the peripheral blood iNKT, as well as their switch from a T helper (Th-2; ie IL-4, IL-13) to Th-1 (ie IFN-γ) cytokine profile. CONCLUSIONS AND CLINICAL RELEVANCE: This study confirms the efficacy and safety of CM-OIT as well as the role of iNKT cells in CM allergy.
BACKGROUND:Cow milk (CM) allergy (CMA) affects up to 3% of the paediatric population and recent data suggest that only about 50% will outgrow by age 8. Oral immunotherapy (OIT) is a type of immune-modulating treatment that is able to induce desensitization to food allergens, to increase tolerance threshold, to reduce the risk of anaphylaxis, and to improve the patient's quality of life. The examination of the immunological changes observed during the establishment of food allergy (FA) desensitization in FA patients is a window into the pathogenesis of food allergy and food tolerance development. In this pathway, we have previously found that invariant natural killer T cells (iNKTs) are involved in CM allergy sensitization and now examine their role in OIT. METHODS: In this study, 10 of the 11 children with CM induced anaphylaxis enrolled in a CMA OIT clinical trial and completed the protocol. Peripheral blood iNKTs were quantitatively and qualitatively via flow cytometry characterized ex vivo and after culture with milk lipids before and after completing the OIT protocol. RESULTS: After completing OIT for CM, children were able to reintroduce CM in their diet. For the first time, we demonstrated that OIT induced a significant increase in the peripheral blood iNKT, as well as their switch from a T helper (Th-2; ie IL-4, IL-13) to Th-1 (ie IFN-γ) cytokine profile. CONCLUSIONS AND CLINICAL RELEVANCE: This study confirms the efficacy and safety of CM-OIT as well as the role of iNKT cells in CM allergy.
Authors: Deborah M Hussey Freeland; Monali Manohar; Sandra Andorf; Benjamin D Hobson; Wenming Zhang; Kari C Nadeau Journal: Semin Immunol Date: 2017-08-31 Impact factor: 11.130
Authors: Uta Jappe; Christian Schwager; Andra B Schromm; Nestor González Roldán; Karina Stein; Holger Heine; Katarzyna A Duda Journal: Front Immunol Date: 2019-02-14 Impact factor: 7.561