Transcript Yael Gernez, MD, PhD-Modulatory effects of Aspergillus

Modulatory effects of Aspergillus colonization
and ABPA on blood and sputum granulocytes in
CF
June 7th, 2012
ECFC, Dublin
Yaël Gernez, MD PhD
Postdoctoral fellow
Richard Moss MD (MD, PI)
Herzenberg’s Laboratory
Stanford University, School of Medicine
CA, USA
ABPA: Background and rationale
• Definition
– Complex hypersensitivity reaction, often in patients with asthma or CF
– Occurs when the bronchi become colonized by Aspergillus fumigatus (Af)
• Incidence
– Colonization with Af : 15% to 60% of CF subjects
– Not all CF patients colonized with Af will develop ABPA (genetic factors?)
• ABPA symptoms and biology: non-specific
– Repeated episodes of bronchial obstruction and inflammation
– Leads to bronchiectasis, fibrosis, and respiratory compromise
Tillie-Leblond et al., Allergy 2005
Goals of this study
Gaps in the clinical management and in the understanding of ABPA
Understanding/Clinical management:
Clinical management:
Tests diagnostic are not optimal:
Not a well understanding about why some
CF-AC develop CF-ABPA and some do not
Literature on ABPA
Hypersensitivity type I
(Higher levels of IgE,
Higher levels of histamine)
CF-airways inflammation : PMN
PNN-protease-bronchiectasies
ABPA-inflammation : PMN+Eos
Try to fill the gaps
Blood basophil activation
assay test
(CD203c, CD63)
Blood and sputum PMN and Eos study
PMN : CD11b, CD63, CD66b
Eos : CD11b, CD63, CD66b, CCR3
Demographics
4 groups of patients were enrolled :
CF patients (without ABPA and/or Af colonization)
CF colonized with Af (2 consecutive positive cultures)
CF and ABPA (4 criteria)
4
26.5
Celiac patients
CD203c levels on blood basophils were primed in CFABPA at baseline, and further increased following 10
minutes of in vitro stimulation
At baseline
Gernez et al., J Cyst Fibros. 2012 May 16
In vitro
CCR3 levels on blood eosinophils were lower in
CF-AC
Eotaxin 1 (CCL11) remained similar between the
3 groups of patients
Eotaxin 3 (CCL26) levels were undectable in the 3 groups of patients (eotaxin 2 NA)
CD66b levels on sputum neutrophils were lower
in CF-ABPA / CF
No changes were observed in blood PMN among the three groups of CF patients
Conclusion
Conclusions
1. CD203c levels are increased at baseline in blood basophils
from CF-ABPA patients
2. CD203c levels are further increased upon stimulation with Af
antigen (extract) in blood basophils from CF-ABPA
3. CD66b levels were lower in sputum neutrophils from CFABPA patients compared to CF and CF-AC.
4. CCR3 levels were lower in blood eosinophils from CF-AC
patients compared to CF and CF-ABPA
PARTICIPANTS:
Patients and their families
Thank you
PI
Richard Moss
Rabindra Tirouvanziam
Lee and Len Herzenberg,
N. HernandezBecker
COLLABORATORS:
Colleen Dunn, Zoe Davies, Cassie Everson
Angela Leung, Cathy Hernandez
FUNDING: Elizabeth Nash Memorial Fellowship
Jeffrey
Walters
Lee and Len
Herzenberg
Rabindra
Tirouvanziam
Richard
Moss
Colleen
Dunn
Cassie
Everson
Zoe
Davies
Cathy
Hernandez