Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis.

Abstract

In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS). PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non-atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients. Demographics, atopic status, asthmatic status, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, Lund-Kennedy nasal endoscopy scores, Lund-Mackay sinus computed tomography (CT) scores, Kennedy Osteitis scores, and GC utilization 6 months postoperatively were collected. Intracellular immunostaining was then performed for functional GC receptor α (GCRα) and nonfunctional GC receptor β (GCRβ), followed by flow cytometry analysis of geometric mean fluorescent intensity (MFI) and the percentage of cells expressing each GC receptor isoform. Compared to controls, each CRS subtype had decreased PBML GCRα and GCRα:GCRβ MFI expression, but no difference in GCRβ expression. Decreasing PBML GCRα in AFRS was associated with increasing Lund-Mackay sinus CT scores (r = -0.880, p =0.004). No significant associations were found between GC receptor isoform expression and other clinical measures. CRS patients have reduced functional PBML GCRα expression and decreased GCRα:GCRβ compared to controls. Reductions in GCRα in AFRS are associated with worsening Lund-Mackay sinus CT scores. The clinical implications of decreased functional GC receptor expression merits further investigation.