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

Abstract

Background Immunoglobulin D (IgD) is an enigmatic antibody isotype best known when co-expressed with IgM on naïve B cells. However, elevated soluble IgD (sIgD) 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 cells 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 ELISA in nasal tissues, nasal lavages, serum, and supernatants of dissociated nasal tissues. IgD+ cells were identified by immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by real-time PCR and multiplex immunoassay. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and the number of IgD+ cells were significantly increased in uncinate tissue (UT) of CRS without nasal polyps (CRSsNP) compared to control (4-fold, P<.05). IgD+ cells were densely scattered in the periglandular regions of CRSsNP UT. We also found that IgD+CD19+CD38bright plasmablasts were significantly elevated in CRSsNP tissues compared to control (P<.05). Among numerous factors tested, IL-2 levels were increased in CRSsNP UT and were positively correlated with tissue IgD levels. Additionally, the supernatants of IL-2-stimulated dissociated CRSsNP tissue had significantly increased sIgD levels compared to IL-2-stimulated dissociated control tissue ex vivo (P<.05). Tissue from CRS patients with preoperative antibiotic use or those with pathogenic bacteria presence showed higher IgD levels compared to tissue from patients absent these variables (P<.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablasts were increased in nasal tissue of CRSsNP. IgD levels were associated with increased IL-2 and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhance mucosal immunity, inflammation, or respond to bacterial infections in CRS, especially CRSsNP.

Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

“…IL‐2 is a nonspecific T‐cell effector that regulates immunity and tolerance, but its role in CRS is poorly defined. A recent study showed that IL‐2 may be associated with elevated immunoglobulin D levels and the presence of pathogenic bacteria in CRSsNP patients . Potential functional relationships between IL‐2 and the olfactory epithelium will require further investigation and confirmation.…”

IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps

“…Using flow cytometry, we confirmed that most polyp IgD 1 CD19 1 B cells were IgM 2 (Fig 2, C), and those IgD 1 IgM 2 B cells were CD38 1 CD138 2 plasmablasts with intracellular IgD expression (see Fig E5 in this article's Online Repository at www.jacionline.org), which is consistent with the previous report. 17 We found that the frequencies of total IgD 1 cells, as well as IgD 1 IgM 2 B cells, in NMCs were increased in both eosinophilic and noneosinophilic polyps, with a more prominent increase in eosinophilic polyps (Fig 2, D). IgD 1 plasmablasts accounted for about 46% and 70% of total IgD 1 cells in eosinophilic and noneosinophilic polyps, respectively.…”

“…14 Recently, 2 studies investigated local IgD expression in patients with CRS, and conflicting results were reported. 17,18 Min et al 17 found increased numbers of mucosal IgD 1 cells in patients with CRSsNP but not those with CRSwNP, 17 whereas Sokoya et al 18 demonstrated enhanced accumulation of IgD 1 cells in both patients with CRSsNP and those with CRSwNP. 18 Nevertheless, more importantly, the specificity and function of IgD have not been explored in those studies.…”

Serum IgD Levels in Allergic Children with Gastrointestinal Manifestations

“…At baseline, IgD levels were significantly higher in the atopic asthma group compared to the control group, and normalized during the next 18 months during asthma treatment [5]. Two very recent publications show a role for IgD in rhinosinusitis [6,7] and suggest that IgD might contribute to enhance mucosal immunity, inflammation, or respond to bacterial infections.…”