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

Mirković, Bojana; Lavelle, Gillian M.; Azim, Ahmed Abdul; Helma, Kristine; Gargoum, Fatma; Molloy, Kevin; Gernez, Yaël; Dunne, Katie; Renwick, J. A. A.; Murphy, Philip G.; Moss, Richard B.; Greene, Catherine M.; Gunaratnam, Cedric; Chotirmall, Sanjay H.; McElvaney, Noel G.

doi:10.1016/j.jaci.2015.07.045

Cited by 52 publications

(49 citation statements)

References 46 publications

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“…Other potential diagnostic tools such as A. fumigatus-specific IgE or IgG to A. fumigatus extract or rAsp f3 and rAsp f4 did not reliably discriminate these groups. A. fumigatus-specific IgE was more commonly elevated in ABPA patients and, elsewhere, we show that in combination with the basophil CD203c activation test, CF-ABPA patients can also be distinguished from A. fumigatus-sensitised patients without ABPA [22]. Finally, analysis of bacterial co-infections revealed a surprising negative association between colonisation with a major bacterial CF pathogen, Staphylococcus aureus, and ABPA.…”

Section: Introductionsupporting

confidence: 59%

“…In the future, it may be advantageous to classify CF or asthma patients by CD203c rather than total IgE level and then compare utility to conventional IgE-based classification. Another limitation of the CD203c BAT is that it may be difficult to discriminate patients sensitised to A. fumigatus from patients with CF-ABPA, but we believe additional analysis of A. fumigatus-specific IgE levels may be able to resolve this issue in most cases [22]. Finally, it has been shown that HRCT can detect pulmonary exacerbations in CF patients [37].…”

Section: Discussionmentioning

confidence: 98%

“…The role of basophils in many clinical conditions including ABPA, however, remains unclear and needs to be explored by further studies. In addition to being a distinguishing feature of ABPA, the association of BAT upregulation of CD203c in combination with specific IgE against A. fumigatus may offer a method to further distinguish CF patients sensitised by A. fumigatus from those with ABPA [22]. While both A. fumigatus sensitisation and ABPA appear to accelerate lung function decline in CF, ABPA is a more serious complication associated with bronchiectasis and other structural lung pathology [2-9, 19, 20].…”

Section: Discussionmentioning

confidence: 99%

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Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

et al. 2015

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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. @ERSpublications Blood basophil surface CD203c level is a method to diagnose ABPA in CF, and study phenotypes, therapy and management http://ow.ly/Sc8zr

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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

et al. 2015

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“…Classifying patients into proposed subgroups and delineating those with ABPA from those who are AF sensitised, AF non-sensitised and those with aspergillus bronchitis [11]. Some studies have provided valuable insights into how AF may influence the progression of CF lung disease [9, 12, 13] however the true extent of the impact on disease progression is unknown.…”

Section: Introductionmentioning

confidence: 99%

Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis

et al. 2017

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BackgroundPulmonary infection is the main cause of death in cystic fibrosis (CF). Aspergillus fumigatus (AF) and Pseudomonas aeruginosa (PA) are the most prevalent fungal and bacterial pathogens isolated from the CF airway, respectively. Our aim was to determine the effect of different colonisation profiles of AF and PA on the clinical status of patients with CF.MethodsA retrospective analysis of data from the Cystic Fibrosis Registry of Ireland from 2013 was performed to determine the effect of intermittent and persistent colonisation with AF or PA or co-colonisation with both microorganisms on clinical outcome measures in patients with CF. Key outcomes measured included forced expiratory volume in one second (FEV1), number of hospitalisations, respiratory exacerbations and antimicrobials prescribed, and complications of CF, including CF related diabetes (CFRD) and allergic bronchopulmonary aspergillosis (ABPA).ResultsThe prevalence of AF and PA colonisation were 11% (5% persistent, 6% intermittent) and 31% (19% persistent, 12% intermittent) in the Irish CF population, respectively. Co-colonisation with both pathogens was associated with a 13.8% reduction in FEV1 (p = 0.016), higher levels of exacerbations (p = 0.042), hospitalisations (p = 0.023) and antimicrobial usage (p = 0.014) compared to non-colonised patients and these clinical outcomes were comparable to those persistently colonised with PA. Intermittent and persistent AF colonisation were not associated with poorer clinical outcomes or ABPA. Patients with persistent PA had a higher prevalence of CFRD diagnosis (p = 0.012).ConclusionsCF patients co-colonised with AF and PA had poor clinical outcomes comparable to patients persistently colonised with PA, emphasising the clinical significance of co-colonisation with these microorganisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0416-4) contains supplementary material, which is available to authorized users.

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“…This group of investigations have also demonstrated that combining a BAT with the CD203c marker and testing for total and specific A. fumigates IgE levels allows for the classification of CF patients into three groups: those who are non-sensitized, those with A. fumigates sensitization without ABPA, and those with ABPA. (28) Thus, a BAT with CD203c as a biomarker may be helpful in the management of CF patients. Previous studies have shown that chitinase activity is increased in the sera and BAL fluid of patients with asthma, COPD, and patients with CF lung disease.…”

Section: Responses To Environmental Fungimentioning

confidence: 99%

Advances in environmental and occupational disorders in 2016

Sheehan

Gaffin

Peden

et al. 2017

Journal of Allergy and Clinical Immunology

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In this review, we highlight recent studies that advance the knowledge and understanding of the effects of various environmental factors and the associated immune responses in patients with allergic diseases. This review will focus on new literature regarding allergic and immune responses to a variety of environmental factors including aeroallergens, stinging insects, fungi, pollutants, viral respiratory infections, climate change, and microbial exposures.

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

Cited by 52 publications

References 46 publications

Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis

Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis

Advances in environmental and occupational disorders in 2016

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