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Modulatory effects of Aspergillus colonization and ABPA on blood and sputum granulocytes in CF

Modulatory effects of Aspergillus colonization and ABPA on blood and sputum granulocytes in CF. June 7 th , 2012 ECFC, Dublin Yaël Gernez, MD PhD Postdoctoral fellow Richard Moss MD (MD, PI) Herzenberg’s Laboratory Stanford University, School of Medicine CA, USA.

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Modulatory effects of Aspergillus colonization and ABPA on blood and sputum granulocytes in CF

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  1. 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

  2. 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

  3. Goals of this study Try to fill the gaps Gaps in the clinical management and in the understanding of ABPA Understanding/Clinical management: Not a well understanding about why some CF-AC develop CF-ABPA and some do not Clinical management: Tests diagnostic are not optimal: 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 Blood basophil activation assay test (CD203c, CD63) Blood and sputum PMN and Eos study PMN : CD11b, CD63, CD66b Eos : CD11b, CD63, CD66b, CCR3

  4. Demographics 4 groups of patients were enrolled : CF patients (without ABPAand/or Af colonization) CF colonized with Af (2 consecutive positive cultures) CF and ABPA (4 criteria) Celiac patients 4 26.5

  5. CD203c levels on blood basophils were primed in CF-ABPA at baseline, and further increased following 10 minutes of in vitro stimulation At baseline In vitro Gernez et al., J Cyst Fibros. 2012 May 16

  6. CCR3 levels on blood eosinophils were lower in CF-AC

  7. 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)

  8. 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

  9. Conclusions Conclusion CD203c levels are increased at baseline in blood basophils from CF-ABPA patients CD203c levels are further increased upon stimulation with Af antigen (extract) in blood basophils from CF-ABPA CD66b levels were lower in sputum neutrophils from CF-ABPA patients compared to CF and CF-AC. CCR3 levels were lower in blood eosinophils from CF-AC patients compared to CF and CF-ABPA

  10. Thank you PARTICIPANTS: Patients and their families PI Richard Moss Rabindra Tirouvanziam Lee and Len Herzenberg, COLLABORATORS: Colleen Dunn, Zoe Davies, Cassie Everson Angela Leung, Cathy Hernandez FUNDING: Elizabeth Nash Memorial Fellowship N. Hernandez-Becker Jeffrey Walters Zoe Davies Lee and Len Herzenberg Rabindra Tirouvanziam Richard Moss Colleen Dunn Cassie Everson Cathy Hernandez

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