Basophil Activation in Aspirin Exacerbated Respiratory Disease

Abstract

Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance of cyclooxygenase-1 (COX-1) enzyme inhibitors. While the underlying pathogenesis is not fully understood, AERD nasal polyps (NP) have been characterized as having an enhanced type-2 inflammatory phenotype. The role that basophils may play in AERD remains unclear and was the focus of the current investigation. NP and peripheral blood was obtained during routine endoscopic sinus surgery from consented AERD patients. CRSwNP patients who were tolerant of COX-1 inhibitors served as controls. Single cell suspensions were prepared from NP or blood and stained for markers of basophil lineage (CD45, FcεRI, CD203c, 2D7) and activation (CD63) for analysis by flow cytometry. The mean number of basophils (CD45+ CD203c+ FcεRI+ CD117-) detected in AERD NP was elevated ∼3-fold compared to CRSwNP (p=0.03). While the number of peripheral blood basophils did not differ between the two conditions (p=0.88), the number of basophils strongly correlated with the number of CD45+ Siglec 8+ eosinophils detected within the same NP specimens (r=0.61, p=0.006). There was a trend toward more basophils having CD63+ co-expression in AERD than CRSwNP NP (p=0.08). In contrast, basophils from AERD NP tended, on average, to have a lower expression of the granule content marker 2D7 than matched peripheral blood or control CRSwNP NP, suggesting greater degranulation in AERD. There is enhanced basophil recruitment and activation in AERD compared to CRSwNP nasal polyps which could contribute to the differences in disease pathogenesis and severity.