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The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis - 05/02/16

Doi : 10.1016/j.jaci.2015.07.045 
Bojana Mirković, PhD a, , Gillian M. Lavelle, BSc a, , Ahmed Abdul Azim, MB, BCh, BAO a, Kristine Helma, MD a, Fatma S. Gargoum, MD a, Kevin Molloy, MB, BCh, BAO a, Yael Gernez, MD, PhD b, Katie Dunne, PhD c, Julie Renwick, PhD c, Philip Murphy, MD c, Richard B. Moss, MD d, Catherine M. Greene, PhD a, Cedric Gunaratnam, MB a, Sanjay H. Chotirmall, MD, PhD e, , Noel G. McElvaney, MD a
a Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland 
b Department of Genetics, Stanford University School of Medicine, Stanford, Calif 
d Center for Excellence in Pulmonary Biology, Department of Paediatrics, Stanford University School of Medicine, Stanford, Calif 
c Clinical Microbiology Department, Trinity College Dublin, the Adelaide and Meath Hospital incorporating the National Children's Hospital, Tallaght, Dublin, Ireland 
e Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 

Corresponding author: Sanjay H. Chotirmall, MD, PhD, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

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.

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Key words : Allergic bronchopulmonary aspergillosis, Aspergillus fumigatus, basophil activation test, body mass index, CD203c, cystic fibrosis, flow cytometry, FEV1, itraconazole, sensitization

Abbreviations used : ABPA, BAT, BMI, CF, GM, ROC, sIgE, sIgG, SPT


Plan


 Supported by Science Foundation Ireland via a United States–Ireland partnership (grant no. SFI/08/US/B1676) and by the US Cystic Fibrosis Foundation.
 Disclosure of potential conflict of interest: P. Murphy has received research support from the National Clinical Research Centre and Crumlin Hospital Dublin, has been supported by a National Children's Hospital joint grant on Metagenomics in Cystic Fibrosis, and is a board member for and has received travel support from Novartis. N. G. McElvaney has received research support from the Health Research Board and Science Foundation Ireland and has received consultancy fees from Chiesi and CSL Behring. The rest of the authors declare that they have no relevant conflicts of interest.


© 2015  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 137 - N° 2

P. 436 - février 2016 Retour au numéro
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