Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Issue 1 (15th November 2012)

• Record Type: Journal Article
• Authors: Gevaert, P.; Nouri‐Aria, K. T.; Wu, H.; Harper, C. E.; Takhar, P.; Fear, D. J.; Acke, F.; De Ruyck, N.; Banfield, G.; Kariyawasam, H. H.; Bachert, C.; Durham, S. R.; Gould, H. J.
• Is Part Of: Allergy. Volume 68:Issue 1(2013:Jan.)
• Page Start: 55
• Page End: 63
• Publication Date: 2012-11-15
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12054
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12054-abs-0001"> <title>Abstract</title> <sec id="all12054-sec-0001" sec-type="section"> <title>Background</title> <p>Chronic rhinosinusitis with nasal polyps (NP) and allergic rhinitis (AR) is characterized by local Th2 inflammation and up‐regulation of IgE; however, IgE in NP is 'polyclonal' and allergen specific, whereas IgE in AR is 'oligoclonal' and allergen specific. Germinal center (GC) reactions occur in AR, while only the formation of GC‐like structures in NP is described. The aim of this study was to investigate the involvement of local IgE production, class switch recombination, and receptor revision in NP.</p> </sec> <sec id="all12054-sec-0002" sec-type="section"> <title>Methods</title> <p>We compared the levels of local IgE, germline gene transcripts, and mature Ig mRNA expression, recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation, and GC reactions in NP tissue <italic>vs</italic> AR and control tissue. Nasal mucosa was immunostained for the co‐expression of RAG1 and RAG2 in B cells, plasma cells, and T cells, using dual or triple immunofluorescence (IF).</p> </sec> <sec id="all12054-sec-0003" sec-type="section"> <title>Results</title> <p>In NP, local IgE level and key markers of local class switching are increased compared with AR and normal controls (NC). In NP, switch circle transcripts reveal ongoing local class switch recombination to IgE. Up to 30% of B cells, plasma cells, and T cells in nasal polyps re‐express both RAG1 and RAG2, required for receptor revision. RAG1 and RAG2 mRNA concentrations are increased in NP and correlated with the magnitude of inflammation and the presence of <italic>S. aureus</italic> enterotoxin (superantigen)‐specific IgE in the nasal polyp mucosa.</p> </sec> <sec id="all12054-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our results provide the first evidence of local receptor revision and class switching to IgE, and B‐cell differentiation into IgE‐secreting plasma cells in NP.</p> </sec> </abstract>