Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors

J Allergy Clin Immunol. 2012 Nov;130(5):1130-1135.e5. doi: 10.1016/j.jaci.2012.05.038. Epub 2012 Jul 15.

Abstract

Background: A recent study of subjects with peanut allergy treated with omalizumab generated some results that were concordant with a study of subjects with cat allergy treated with omalizumab. However, there were differences that provided additional insight into the nature of the cellular responses in allergic subjects.

Objective: We sought to determine the cause for failure to suppress the allergen-induced basophil response during treatment with omalizumab.

Methods: Patients with peanut allergy were treated with omalizumab. Clinical, serologic, and cellular indices relevant to the response of the subjects and their peripheral blood basophil values (specific/total IgE ratio, cell-surface FcεRI expression, and histamine release responses to anti-IgE antibody or peanut allergen) were obtained at 3 times.

Results: After treatment, approximately 60% of the subjects' basophil responses to peanut allergen did not significantly decrease. In 40% of cases, the in vitro basophil response to peanut allergen increased 2- to 7-fold. The increases were associated with 2 primary factors: a high (>10%) specific/total IgE ratio and an increase in the intrinsic response of the basophil to IgE-mediated stimulation. The extent to which the basophil response to peanut allergen increased was inversely correlated with improvement in the patient's ability to tolerate ingestion of peanut.

Conclusion: The basophil response during treatment with omalizumab is a consequence of 2 competing factors: suppression of allergen-specific IgE on the cell surface versus increased intrinsic sensitivity to IgE-mediated stimulation. In subjects with peanut allergy, the basophil response appears to mitigate against the ability of omalizumab to improve the patient's tolerance of oral allergen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Allergens / immunology
  • Animals
  • Anti-Allergic Agents / administration & dosage*
  • Anti-Allergic Agents / adverse effects
  • Antibodies, Anti-Idiotypic / administration & dosage*
  • Antibodies, Anti-Idiotypic / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Cells, Cultured
  • Female
  • Follow-Up Studies
  • Histamine / metabolism
  • Humans
  • Immunoglobulin E / blood*
  • Male
  • Omalizumab
  • Peanut Hypersensitivity / immunology
  • Peanut Hypersensitivity / therapy*
  • Receptors, IgE / metabolism*
  • Treatment Outcome

Substances

  • Allergens
  • Anti-Allergic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • FcepsilonRI alpha-chain, human
  • Receptors, IgE
  • Omalizumab
  • Immunoglobulin E
  • Histamine