The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis

J Allergy Clin Immunol. 2016 Feb;137(2):436-443.e9. doi: 10.1016/j.jaci.2015.07.045. Epub 2015 Sep 18.

Abstract

Background: Colonization by Aspergillus fumigatus in patients with cystic fibrosis (CF) can cause A fumigatus sensitization and/or allergic bronchopulmonary aspergillosis (ABPA), which affects pulmonary function and clinical outcomes. Recent studies show that specific allergens upregulate the surface-expressed basophil marker CD203c in sensitized subjects, a response that can be readily measured by using flow cytometry.

Objective: We sought to identify A fumigatus sensitization in patients with CF by using the basophil activation test (BAT).

Methods: Patients with CF attending Beaumont Hospital were screened for study inclusion. BAT was used to identify A fumigatus sensitization. Serologic (total and A fumigatus-specific IgE), pulmonary function, and body mass index measurements were performed.

Results: The BAT discriminates A fumigatus-sensitized from nonsensitized patients with CF. Persistent isolation of A fumigatus in sputum is a significant risk factor for A fumigatus sensitization. Levels of the A fumigatus-stimulated basophil activation marker CD203c inversely correlated with pulmonary function and body mass index in A fumigatus-sensitized but not nonsensitized patients with CF. Total and A fumigatus-specific IgE, but not IgG, levels are increased in A fumigatus-sensitized patients with CF and ABPA when compared with those in A fumigatus-sensitized and nonsensitized patients with CF without ABPA. Itraconazole treatment did not affect A fumigatus sensitization.

Conclusion: Combining the BAT with routine serologic testing allows classification of patients with CF into 3 groups: nonsensitized, A fumigatus-sensitized, and ABPA. Accurate and prompt identification of A fumigatus-associated clinical status might allow early and targeted therapeutic intervention, potentially improving clinical outcomes.

Keywords: Allergic bronchopulmonary aspergillosis; Aspergillus fumigatus; CD203c; FEV(1); basophil activation test; body mass index; cystic fibrosis; flow cytometry; itraconazole; sensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Specificity / immunology
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Antigens, Fungal / immunology
  • Antigens, Surface / metabolism
  • Aspergillosis / diagnosis
  • Aspergillosis / drug therapy
  • Aspergillosis / etiology*
  • Aspergillosis / metabolism*
  • Aspergillus / immunology*
  • Basophils / immunology
  • Basophils / metabolism*
  • Biomarkers
  • Body Mass Index
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / physiopathology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunophenotyping
  • Leukocyte Count
  • Male
  • Phosphoric Diester Hydrolases / metabolism*
  • Prospective Studies
  • Pyrophosphatases / metabolism*
  • Sputum / immunology
  • Sputum / microbiology

Substances

  • Antifungal Agents
  • Antigens, Fungal
  • Antigens, Surface
  • Biomarkers
  • ENPP3 protein, human
  • Immunoglobulin G
  • Immunoglobulin E
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases