title: Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis.
abstract: The diagnosis of cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) is clinically challenging, due to the absence of an objective biological test. Since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between CF patients with and without ABPA.We conducted a prospective longitudinal study (Stanford cohort) comparing basophil activation test CD203c levels by flow cytometry before and after activation with Aspergillus fumigatus allergen extract or recombinant Asp f1 in 20 CF patients with ABPA (CF-ABPA) and in two comparison groups: CF patients with A. fumigatus colonisation (AC) but without ABPA (CF-AC; n=13) and CF patients without either AC or ABPA (CF; n=12). Patients were tested every 6 months and when ill with pulmonary exacerbation. We also conducted cross-sectional validation in a separate patient set (Dublin cohort).Basophil CD203c surface expression reliably discriminated CF-ABPA from CF-AC and CF over time. Ex vivo stimulation with A. fumigatus extract or recombinant Asp f1 produced similar results within the Stanford (p<0.0001) and the Dublin cohorts. CF-ABPA patients were likelier to have elevated specific IgE to A. fumigatus and were less frequently co-infected with Staphylococcus aureus.Basophil CD203c upregulation is a suitable diagnostic and stable monitoring biomarker of ABPA in CF.
authors.affiliation: Dept of Genetics, Stanford University School of Medicine, Stanford, CA, USA Dept of Allergy and Immunology, Mount Sinai Hospital, New York, NY, USA These authors contributed equally to this work.
authors.forename: Yael
authors.initials: Y
authors.lastname: Gernez
authors.affiliation: Dept of Genetics, Stanford University School of Medicine, Stanford, CA, USA These authors contributed equally to this work.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Waters
authors.affiliation: Respiratory Research Division, Dept of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Bojana
authors.identifier: 0000-0002-2128-6779
authors.initials: B
authors.lastname: Mirković
authors.affiliation: Respiratory Research Division, Dept of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Lavelle
authors.affiliation: Center for Excellence in Pulmonary Biology, Dept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Dunn
authors.affiliation: Center for Excellence in Pulmonary Biology, Dept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Davies
authors.affiliation: Center for Excellence in Pulmonary Biology, Dept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Cassie
authors.initials: C
authors.lastname: Everson
authors.affiliation: Center for CF and Airways Disease Research, Dept of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Tirouvanziam
authors.affiliation: Laurelton Research, Oakland, CA, USA.
authors.forename: Elana
authors.initials: E
authors.lastname: Silver
authors.affiliation: Mount Sinai School of Medicine, Dept of Preventive Medicine, New York, NY, USA.
authors.forename: Sylvan
authors.initials: S
authors.lastname: Wallenstein
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Sanjay H
authors.identifier: 0000-0003-0417-7607
authors.initials: SH
authors.lastname: Chotirmall
authors.affiliation: Respiratory Research Division, Dept of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
authors.affiliation: Dept of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
authors.affiliation: Center for Excellence in Pulmonary Biology, Dept of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA rmoss@stanford.edu.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Moss
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000276:immunology; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002353:Carrier State / Q000175:diagnosis / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011446:Prospective Studies; D055732:Pulmonary Aspergillosis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000485:Allergens; D015415:Biomarkers; C427944:ENPP3 protein, human; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases