Abstract

Rationale: Eosinophilia is an important biomarker for tracking disease severity and the response to therapy in asthmatic patients. However, differences in response to therapy between circulating and airway eosinophils highlight the need to characterize eosinophil phenotypes.

Methods: 11 mild allergic asthmatics underwent inhaled allergen and diluent challenges. Whole blood and sputum samples were collected 24hr before challenge and post-challenge at 7hr and 24hr, and stained for eosinophils (CD45+ CD16- CD15+) and surface receptors for cytokines CD125, CD123; chemokines; adhesion molecules VLA-4 (CD49d), L-selectin (CD62L); immunoregulatory receptor Siglec 8; and activation markers (CD66b, CD63, CD69). Eosinophils +ve for each receptor were expressed as a % of total eosinophils.

Results: At baseline there was a higher % of eosinophils +ve for CD123, CD62L, CD49d, Siglec 8, CCR3, CD63 and CD69 in blood compared to sputum.  Allergen challenge reduced FEV1 by ? 20%. Post-allergen challenge, the % of Siglec 8 +ve eosinophils increased in sputum compared to diluent (p<0.05).  Compared to pre-allergen baseline the % eosinophils +ve for CD69 and CD123 increased in blood, and CD123 decreased in sputum post-allergen, but these changes were not significantly different than diluent. 

Conclusion: Receptors to ligands for eosinophil activation and recruitment are downregulated in sputum eosinophils, confirming previous activation of these pathways.  Recruitment of Siglec 8 +ve eosinophils to airways post-allergen challenge may be a mechanism for local immunoregulation.