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Review

An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens

by
Thomas A. E. Platts-Mills
1,*,
Behnam Keshavarz
1,
Jeffrey M. Wilson
1,
Rung-chi Li
1,
Peter W. Heymann
1,
Diane R. Gold
2,3,
Emily C. McGowan
1 and
Elizabeth A. Erwin
4
1
Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
2
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
3
Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4
Division of Allergy and Immunology, Nationwide Children’s Hospital, Columbus, OH 43205, USA
*
Author to whom correspondence should be addressed.
Children 2021, 8(5), 418; https://doi.org/10.3390/children8050418
Submission received: 5 April 2021 / Revised: 15 May 2021 / Accepted: 16 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Clinical Research and Recent Advances in Paediatric Allergic Diseases)
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Abstract

Antibodies of the IgG4 isotype are strongly associated with allergic disease but have several properties such as not precipitating with allergens, not activating complement and poor binding to Fcγ receptors that argue against a pro-inflammatory role. In keeping with that, IgG4 antibodies are a striking feature of the response to immunotherapy. In two naturally occurring situations IgG4 antibodies are common with low or absent IgE antibodies. The first example is children raised in a house with a cat and the second is eosinophilic esophagitis (EoE). In many population-based cohorts, the ownership of a cat in early childhood is associated with a decreased prevalence of a cat allergy at age 10. The second example (i.e., EoE) is a novel form of food allergy that is not mediated by IgE and is related to consuming cow’s milk or wheat. In EoE, patients have IgG4 to milk proteins in high > 10 µg/mL or very high > 100 µg/mL titers. Enigmatically these patients are found to have deposits of IgG4 in the wall of their inflamed esophagus. The factors that have given rise to EoE remain unclear; however, changes in food processing over the past 50 years, particularly ultra-heat treatment and the high pressure homogenization of milk, represent a logical hypothesis.
Keywords: food allergy; IgG4 antibody; Fab-arm exchange; eosinophilic esophagitis; milk; wheat; food processing food allergy; IgG4 antibody; Fab-arm exchange; eosinophilic esophagitis; milk; wheat; food processing

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MDPI and ACS Style

Platts-Mills, T.A.E.; Keshavarz, B.; Wilson, J.M.; Li, R.-c.; Heymann, P.W.; Gold, D.R.; McGowan, E.C.; Erwin, E.A. An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens. Children 2021, 8, 418. https://doi.org/10.3390/children8050418

AMA Style

Platts-Mills TAE, Keshavarz B, Wilson JM, Li R-c, Heymann PW, Gold DR, McGowan EC, Erwin EA. An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens. Children. 2021; 8(5):418. https://doi.org/10.3390/children8050418

Chicago/Turabian Style

Platts-Mills, Thomas A. E., Behnam Keshavarz, Jeffrey M. Wilson, Rung-chi Li, Peter W. Heymann, Diane R. Gold, Emily C. McGowan, and Elizabeth A. Erwin. 2021. "An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens" Children 8, no. 5: 418. https://doi.org/10.3390/children8050418

APA Style

Platts-Mills, T. A. E., Keshavarz, B., Wilson, J. M., Li, R.-c., Heymann, P. W., Gold, D. R., McGowan, E. C., & Erwin, E. A. (2021). An Overview of the Relevance of IgG4 Antibodies in Allergic Disease with a Focus on Food Allergens. Children, 8(5), 418. https://doi.org/10.3390/children8050418

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