Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab

Mucosal Immunol. 2012 May;5(3):267-76. doi: 10.1038/mi.2012.5. Epub 2012 Feb 8.

Abstract

Food allergy is a major public health problem, for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cow's milk allergy undergoing a novel and rapid high-dose oral desensitization protocol enabled by treatment with omalizumab (anti-immunoglobulin (Ig)E monoclonal antibodies). Within a week of treatment, the CD4(+) T-cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4(+) T cells. Over the following 3 months while the subjects remained on high doses of daily oral milk, the CD4(+) T-cell response returned, characterized by a shift from interleukin-4 to interferon-γ production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high-dose oral allergen desensitization may be associated with deletion of allergen-specific T cells, without the apparent development of allergen-specific Foxp3(+) regulatory T cells.

Trial registration: ClinicalTrials.gov NCT00968110.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Allergens / administration & dosage*
  • Allergens / adverse effects
  • Animals
  • Antibodies, Anti-Idiotypic / administration & dosage
  • Antibodies, Anti-Idiotypic / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cattle
  • Cells, Cultured
  • Child
  • Desensitization, Immunologic / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin E / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Lymphocyte Count
  • Male
  • Milk / adverse effects
  • Milk Hypersensitivity / immunology
  • Milk Hypersensitivity / therapy*
  • Milk Proteins / administration & dosage*
  • Milk Proteins / adverse effects
  • Omalizumab
  • Th1-Th2 Balance

Substances

  • Allergens
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Milk Proteins
  • Interleukin-4
  • Omalizumab
  • Immunoglobulin E
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00968110