Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Abstract

Background: IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD⁺IgM^- B-cell populations have been described in the human upper respiratory mucosa.

Objective: We assessed whether levels of sIgD and IgD⁺ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD⁺ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels.

Methods: sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD⁺ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records.

Results: sIgD levels and numbers of IgD⁺ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P < .05). IgD⁺ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD⁺CD19⁺CD38^bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P < .05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2-stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2-stimulated dissociated control tissue ex vivo (P < .05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P < .05).

Conclusion: sIgD levels and IgD⁺CD19⁺CD38^bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

Keywords: B cells; Chronic rhinosinusitis; IL-2; IgD; bacterial infection; mucosal immunity.