EXPRESSION OF IGE HEAVY-CHAIN TRANSCRIPTS IN THE SINUS MUCOSA OF ATOPIC AND NONATOPIC PATIENTS WITH CHRONIC SINUSITIS

We have recently shown the increased mRNA expression of interleukin (I L)-4 and IL-13 in sinus biopsies from allergic subjects with chronic s inusitis (ACS), whereas only IL-13 mRNA was elevated in biopsies obtai ned from nonallergic subjects with chronic sinusitis (NCS). In the lym ph nodes and spleen, these cytokines may promote IgE production throug h transcriptional activation of the germline IgE heavy chain promoter, an event which precedes immunoglobulin isotype switching to IgE in B cells. We hypothesized that local expression of IL-4 and/or IL-13 migh t act by inducing germline IgE heavy chain transcript expression local ly in the sinus mucosa of chronic sinusitis patients, Mucosal sinus bi opsies were obtained from 13 patients with ACS, 12 subjects with NCS, and 11 normal control individuals. The numbers of B cells in the sinus mucosa were studied by immunocytochemistry with anti-CD20 monoclonal antibodies, In situ hybridization was performed using antisense radiol abeled riboprobes complementary to the IgE epsilon-heavy chain germlin e (I epsilon) and heavy chain constant region (C epsilon) gene transcr ipts. Riboprobes specific for the IgG gamma-heavy chain constant regio n (C gamma) were used as an isotype control. Immunocytochemical analys is indicated augmented numbers of CD20-positive B cells in the biopsie s obtained from ACS patients compared with NCS subjects (P < 0.05) and normal control subjects (P < 0.01). Statistically significant increas es were observed in the numbers of cells expressing I epsilon and C ep silon transcripts in the sinus mucosa of ACS patients compared with th ose with NCS (P < 0.001) and normal controls (P < 0.001), while C gamm a RNA expression did not differ significantly between the groups. In t hree randomly selected ACS biopsies, 92-100% of cells expressing C eps ilon transcripts and 100% of I epsilon RNA-positive cells coexpressed CD20 immunoreactivity. Cells expressing C epsilon transcripts were als o significantly increased in NCS compared with normal controls (P < 0. 05). The results of this study suggest that local IgE class switching occurs in the pathogenesis of ACS and that ACS and NCS are both associ ated with increased expression of C epsilon transcripts.