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 (IL)-4 and IL-13 in sinus biopsies from allergic subjects with chronic sinusitis (ACS), whereas only IL-13 mRNA was elevated in biopsies obtained from nonallergic subjects with chronic sinusitis (NCS). In the lymph nodes and spleen, these cytokines may promote IgE production through 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 might act by inducing germline IgE heavy chain transcript expression locally in the sinus mucosa of chronic sinusitis patients. Mucosal sinus biopsies 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 radiolabeled riboprobes complementary to the IgE epsilon -heavy chain germline (Iepsilon) and heavy chain constant region (Cepsilon) gene transcripts. Riboprobes specific for the IgG gamma-heavy chain constant region (Cgamma) were used as an isotype control. Immunocytochemical analysis indicated augmented numbers of CD20-positive B cells in the biopsies obtained from ACS patients compared with NCS subjects (P < 0.05) and normal control subjects (P < 0.01). Statistically significant increases were observed in the numbers of cells expressing Iepsilon and Cepsilon transcripts in the sinus mucosa of ACS patients compared with those with NCS (P < 0. 001) and normal controls (P < 0.001), while Cgamma RNA expression did not differ significantly between the groups. In three randomly selected ACS biopsies, 92-100% of cells expressing Cepsilon transcripts and 100% of Iepsilon RNA-positive cells coexpressed CD20 immunoreactivity. Cells expressing Cepsilon transcripts were also 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 associated with increased expression of Cepsilon transcripts.
Ghaffar
O
O
Meakins-Christie Laboratories, SMBD-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Durham
S R
SR
Al-Ghamdi
K
K
Wright
E
E
Small
P
P
Frenkiel
S
S
Gould
H J
HJ
Hamid
Q
Q
D000328:Adult; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012852:Sinusitis / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic / Q000502:physiology
D018951:Antigens, CD20; D007143:Immunoglobulin Heavy Chains; D007139:Immunoglobulin epsilon-Chains; D007142:Immunoglobulin gamma-Chains; D012333:RNA, Messenger; D007073:Immunoglobulin E