Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy - 04/07/18
, Alexander Grishin, PhD a, ∗, Madhan Masilamani, PhD a, ∗, Donald Y.M. Leung, MD, PhD b, Scott H. Sicherer, MD a, Stacie M. Jones, MD c, A.Wesley Burks, MD d, Alice K. Henning, MS e, Peter Dawson, PhD e, Joanna Grabowska, MS a, Charuta Agashe, MS a, Wendy F. Davidson, PhD f, Robert A. Wood, MD g, Hugh A. Sampson, MD aAbstract |
Background |
Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown.
Objectives |
We sought to study egg-specific antibody, basophil, and T-cell responses in children with reactivity or tolerance to BE.
Methods |
All participants underwent double-blind, placebo-controlled challenges to BE, and those who tolerated BE were challenged with unheated egg white protein to confirm clinical egg reactivity. Laboratory studies included serum antibody measurements, basophil activation tests, and CD154-based detection of egg-responsive T cells by using flow cytometry.
Results |
Of the 129 children studied, BE-reactive participants had significantly greater levels of egg-, ovalbumin-, and ovomucoid-specific IgE; lower ratios of egg-specific IgG4/IgE; and increased basophil activation in response to egg. Among all participants, CD154-based profiling revealed egg-responsive T cells producing IL-4 and IL-13 but little IL-10 or IFN-γ, as well as the presence of egg-responsive Foxp3+CD25+CD127low regulatory T cells. Egg-responsive T cells expressed CCR4, CCR6, and CXCR5, indicating capacity for homing to the skin, mucosa, and B-cell follicles. However, neither the frequency nor phenotype of egg-responsive T cells was different in those with tolerance or reactivity to BE.
Conclusions |
Egg-specific antibody and basophil responses, but not T-cell responses, are greater in those with reactivity versus tolerance to BE. Egg-specific antibody and T-cell responses were highly heterogeneous in this cohort. The clinical implications of this immune heterogeneity will need to be studied longitudinally.
Le texte complet de cet article est disponible en PDF.Key words : Egg allergy, food allergy, IgE, IgG4, basophil, CD4+ T lymphocyte, regulatory T cell, TH2
Abbreviations used : BE, OFC, Treg
Plan
| Supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases grants U19AI066738 and U01AI066560. The project was also supported by grant numbers UL1 TR000154 (National Jewish Health), UL1 TR000067 (Mount Sinai), UL1 TR000039 (Arkansas), UL1 TR000083 (North Carolina), and UL1 TR000424 (Johns Hopkins) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). |
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| Disclosure of potential conflict of interest: M. C. Berin has received a grant from the National Institute of Allergy and Infectious Diseases. A. Grishin has received a grant from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) and has consultant arrangements with N-Fold. S. H. Sicherer has received a grant from the NIAID and HAL Allergy and receives personal fees from the American Academy of Allergy, Asthma & Immunology and UpToDate. S. M. Jones is on the Research Advisory Board for Food Allergy Research and Education (FARE); has consultant arrangements with Aimmune Therapeutics; has received grants from Aimmune Therapeutics, DBV Technologies, Astellas, FARE, the National Peanut Board, the NIH/NIAID Immune Tolerance Network and the NIH/NIAID Consortium of Food Allergy Research; and has received payment from EMMES Corporation for CSR review/preparation for DBV Technologies. A. W. Burks has received personal fees from the NIH AITC Review Panel, Allertein, the American Society for Microbiology, Elsevier, FARE, the World Allergy Organization, Adept Field Solutions, Aimmune Therapeutics, Astellas Pharma Global Development, Biomerica, Evelo Biosceinces/Epiva Biosciences, First Manhattan, Genentech, GLG Research, Insys Therapeutics, Intrommune Therapeutics, PPD Development, Regeneron Pharmaceuticals, Sanofi US Services, SRA International, Stallergenes, UKKO, and Valeant Pharmaceuticals North America and has received grants from FARE, the NIH, and the Wallace Research Foundation. A. K. Henning has received a grant from the NIH. P. Dawson has received a grant from the Division of Allergy, Immunology and Transplantation, NIH. R. A. Wood has received grants from Aimmune, DBV Technologies, and Astellas. H. A. Sampson has received a grant from the NIH/NIAID and is employed by and has received stock/stock options from DBV Technologies. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 1
P. 149 - juillet 2018 Retour au numéro
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