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Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow’s milk tolerance - 27/12/12

Doi : 10.1016/j.jaci.2012.06.003 
Lara S. Ford, MD, MPH a, Katherine A. Bloom, MD a, Anna H. Nowak-Węgrzyn, MD a, Wayne G. Shreffler, MD, PhD b, Madhan Masilamani, PhD a, Hugh A. Sampson, MD a,
a Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 
b Massachusetts General Hospital, Boston, Mass 

Corresponding author: Hugh A. Sampson, MD, Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1198, New York, NY 10029.

Abstract

Background

In our previous study about 75% of children with cow’s milk allergy tolerated baked milk products, which improved their prognosis and quality of life.

Objective

We sought to identify biomarkers of varying degrees of clinical tolerance among a cohort of children with cow’s milk allergy.

Methods

One hundred thirty-two subjects were initially classified as baked milk–reactive, baked milk–tolerant, or having “outgrown milk allergy” based on the results of oral food challenges. The baked milk–tolerant group was then divided into 3 groups based on the amount and degree of heat-denatured milk protein that they could tolerate. Serum was analyzed for allergen-specific IgE and IgG4 levels, basophil reactivity was assessed in whole blood stimulated with serial 10-fold dilutions of milk protein, and skin prick tests (SPTs) were performed to commercial milk extract. Activated basophils were defined by using flow cytometry as CD63brightCD203c+CD123+HLA-DRdim/−CD41alineage. Data were analyzed by using the Jonckheere-Terpstra test.

Results

Significant differences across the 5 clinical groups were seen for median casein- and milk-specific IgE levels, casein-specific IgG4 levels, and casein IgE/IgG4 ratios; milk-specific to nonspecific basophil activation ratio, median basophil reactivity, and spontaneous basophil activation (CD203c expression after stimulation with RPMI); and milk SPT wheal diameters. Casein- and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to baked milk than among those who tolerate it.

Conclusions

The majority of patients with milk allergy are able to tolerate some forms of baked milk in their diets. Different phenotypes of children with cow’s milk allergy can be distinguished by casein- and milk-specific IgE levels, milk-specific basophil reactivity, and milk SPT mean wheal diameters. Spontaneous basophil activation is greater among patients with more severe clinical milk reactivity.

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Key words : Cow’s milk allergy, tolerance, extensively heated, baked, immunotherapy, immunomodulation, biomarker, basophil activation

Abbreviation used : SPT


Esquema


 H.A.S. is funded in part by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI44236 and AI066738) and the National Center for Research Resources (RR026134). L.S.F. is funded by the AAAAI/Elliot and Roslyn Jaffe Third-Year Fellowship Food Allergy Research Award at Mount Sinai School of Medicine.
 Disclosure of potential conflict of interest: L. S. Ford has received research support from the American Academy of Allergy, Asthma & Immunology (AAAAI) Jaffe Third-Year Fellowship Food Allergy Research Award and is chair of the AAAAI Fellow-in-Training Committee. H. A. Sampson is a consultant for Allertein Therapeutics, LLC; is on the advisory board for Immusan T and Novartis; has received research support from the Food Allergy Initiative (FAI) and the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH); is a consultant and scientific advisor for the FAI; is a medical advisor for the Food Allergy & Anaphylaxis Network; is a scientific advisor for the University of Nebraska–FARRP; and is 45% owner of Herb Springs, LLC. The rest of the authors declare that they have no relevant conflicts of interest.


© 2012  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 131 - N° 1

P. 180 - janvier 2013 Regresar al número
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