Diversity of immunoglobulin E-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis

Abstract

The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4 ± 3.2%; CRS, 7.0 ± 4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE. We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease.