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Spontaneous food allergy in Was −/− mice occurs independent of Fcε RI ‐mediated mast cell activation
Author(s) -
Lexmond W. S.,
Goettel J. A.,
Sallis B. F.,
McCann K.,
Rings E. H. H. M.,
JensenJarolim E.,
Nurko S.,
Snapper S. B.,
Fiebiger E.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13219
Subject(s) - mast cell , allergy , food allergy , immunology , food allergens , chemistry , medicine
Background Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant‐free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott‐Aldrich syndrome ( WAS ) and defined whether spontaneous disease in Was −/− mice recapitulates the pathology of a conventional disease model and/or human food allergy. Methods Comparative Immuno CAP ISAC microarray was performed in patients with food allergy or WAS . Spontaneous food allergy in Was −/− mice was compared to an adjuvant‐based model in wild‐type mice ( WT ‐ OVA /alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high‐affinity IgE Fc receptor (Fcε RI ) in allergic sensitization was evaluated using Was −/− Fcer1a −/− mice. Results Polysensitization to food was detected in both WAS and food‐allergic patients which was recapitulated in the Was −/− model. Oral administration of ovalbumin (OVA) in Was −/− mice induced low titers of OVA ‐specific IgE compared to the WT ‐ OVA /alum model. Irrespectively, 79% of Was −/− mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was −/− mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of Fcε RI expression on mast cells (MCs) and basophils. Conclusions Was −/− mice provide a model of food allergy with the advantage of mimicking polysensitization and low food‐antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/Fcε RI activation cascade will not affect sensitization to food.