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Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis - 04/07/18

Doi : 10.1016/j.jaci.2018.02.049 
Alexander J. Schuyler, BS, BA a, , Jeffrey M. Wilson, MD, PhD a, , Anubha Tripathi, MD a, Scott P. Commins, MD, PhD b, Princess U. Ogbogu, MD c, Patrice G. Kruzsewski, DO d, Barrett H. Barnes, MD e, Emily C. McGowan, MD, PhD a, Lisa J. Workman, BA a, Jonas Lidholm, PhD f, Sheryl L. Rifas-Shiman, MPH g, Emily Oken, MD, MPH g, Diane R. Gold, MD, MPH h, Thomas A.E. Platts-Mills, MD, PhD a, , , Elizabeth A. Erwin, MD i, ,
a Division of Allergy & Clinical Immunology, University of Virginia, Charlottesville, Va 
e Division of Pediatric Gastroenterology, University of Virginia, Charlottesville, Va 
b Division of Rheumatology, Allergy & Immunology, University of North Carolina, Chapel Hill, NC 
c Allergy and Immunology, Department of Otolaryngology, The Ohio State University Wexner Medical Center, Columbus, Ohio 
d Division of Pediatric Gastroenterology, Hepatology & Nutrition, Emory University, Atlanta, Ga 
f Thermo Fisher Scientific, Uppsala, Sweden 
g Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 
h Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass 
i Center for Innovation in Pediatric Practice, Nationwide Children's Hospital, Columbus, Ohio 

Corresponding author: Thomas A. E. Platts-Mills, MD, PhD, Asthma and Allergic Diseases Center, University of Virginia, PO Box 801355, Charlottesville, VA 22908-1355.Asthma and Allergic Diseases CenterUniversity of VirginiaPO Box 801355CharlottesvilleVA22908-1355∗∗Elizabeth A. Erwin, MD, Center for Innovation in Pediatric Practice, Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH 43205-2664.Center for Innovation in Pediatric PracticeNationwide Children's Hospital700 Children's DrColumbusOH43205-2664

Abstract

Background

Allergen-specific IgG4 (sIgG4) antibodies are often associated with tolerance, but sIgG4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG4 are not well established in the general pediatric population.

Objective

We sought to investigate serum food sIgG4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG4 levels.

Methods

Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins.

Results

In the EoE cohort high-titer sIgG4 (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG4/sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys.

Conclusions

sIgG4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE.

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Graphical abstract




Le texte complet de cet article est disponible en PDF.

Key words : Eosinophilic esophagitis, children, IgG4 assays, cow's milk proteins, molecular allergens

Abbreviations used : CM, CSR, EoE, α-gal, hpf, ISAC, OR, sIgE, sIgG4


Plan


 Supported by funding from National Institutes of Health grants R01-AI-20565 (to T.A.E.P-M.) and K23-AI-059317 (to E.A.E.). Project Viva is supported by grants R01-AI-102960 and R01-HD-034568.
 Disclosure of potential conflict of interest: E. C. McGowan received grant KAI123596A for this work from National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases. J. Lidholm is employed by Thermo Fisher Scientific. S. L. Rifas-Shiman's and E. Oken's institutions received a grant from the NIH for this work. D. R. Gold's institution received a grant and support for travel from NIH for this work. T. A. E. Platts-Mills received a grant from the NIH and support from Phadia/Thermo Fisher during the conduct of the study. E. A. Erwin received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 142 - N° 1

P. 139 - juillet 2018 Retour au numéro
Article précédent Article précédent
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