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Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy - 15/08/11

Doi : 10.1016/j.jaci.2008.12.1128 
Niya Wanich, MD a, Anna Nowak-Wegrzyn, MD a, Hugh A. Sampson, MD a, b, Wayne G. Shreffler, MD, PhD a, b,
a Division of Allergy and Immunology, Department of Pediatrics, the Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 
b Immunology Institute, Mount Sinai School of Medicine, New York, NY 

Reprint requests: Wayne G. Shreffler, MD, PhD, Division of Pediatric Allergy and Immunology, Department of Pediatrics, Box 1198, One Gustave L Levy Place, New York, NY 10029.

Abstract

Background

Children with milk allergy who tolerate heat-denatured milk (HM) have less severe reactions and outgrow the condition earlier than those who react to HM, which might be related to differences in IgE-dependent effector cell function.

Objective

We sought to apply a novel assay to test the hypothesis that HM-tolerant children have suppressed IgE-mediated basophil responses.

Methods

Allergic, HM-tolerant, outgrown, or control subjects were defined based on oral food challenges. Whole blood cells were stimulated in vitro with a range of milk allergen doses in the presence or absence of autologous serum or with dilutions of autologous serum. Activated basophils were identified by means of flow cytometry as CD63brightCD123+CD203c+HLA-DRCD41a.

Results

HM-tolerant subjects’ basophils were significantly less responsive to milk allergen stimulation at all doses than were basophils from HM-reactive (allergic) individuals. In the absence of autologous serum, HM-tolerant subjects’ basophils were significantly more reactive at low allergen concentrations. To a lesser extent, autologous serum also inhibited IL-3– and anti-IgE–induced, but not N-formyl-methionyl-leucyl-phenylalanine–induced, responses. The allergen-specific responsiveness of HM-tolerant subjects’ basophils increased with dilution of autologous serum with normal pooled serum.

Conclusion

Children with milk allergy with a favorable prognosis have evidence of extrinsically suppressed allergen-specific effector cell reactivity.

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Key words : Milk allergy, basophils, basophil activation test, oral tolerance, cow’s milk allergy

Abbreviations used : fMLP, HM, PI3K


Plan


 Supported in part by the National Institute of Allergy and Infectious Diseases (U19 AI-44236) and the National Center for Research Resources (M01-RR-00071). W.S. is supported by a Pediatric National Institutes of Health-Loan Repayment Program award.
 Disclosure of potential conflict of interest: A. Nowak-Wegrzyn has received research support from Novartis Vaccines. H. A. Sampson is a consultant and shareholder of Allertein Therapeutics, LLC; has received research support from the Food Allergy Initiative and the National Institute of Allergy and Infectious Diseases/National Institutes of Health; is a consultant/scientific advisor to the Food Allergy Initiative; is president of the American Academy of Allergy, Asthma & Immunology; and is a partial owner of Herbal Springs, LLC. The rest of the authors have declared that they have no conflict of interest.


© 2009  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 123 - N° 4

P. 789 - avril 2009 Retour au numéro
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