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.
Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps
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Media type:
E-Article
Title:
Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps
Contributor:
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.
imprint:
Wiley, 2013
Published in:Allergy
Language:
English
DOI:
10.1111/all.12054
ISSN:
0105-4538;
1398-9995
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Chronic rhinosinusitis with nasal polyps (<jats:styled-content style="fixed-case">NP</jats:styled-content>) and allergic rhinitis (<jats:styled-content style="fixed-case">AR</jats:styled-content>) is characterized by local Th2 inflammation and up‐regulation of IgE; however, IgE in <jats:styled-content style="fixed-case">NP</jats:styled-content> is ‘polyclonal’ and allergen specific, whereas IgE in <jats:styled-content style="fixed-case">AR</jats:styled-content> is ‘oligoclonal’ and allergen specific. Germinal center (<jats:styled-content style="fixed-case">GC</jats:styled-content>) reactions occur in <jats:styled-content style="fixed-case">AR</jats:styled-content>, while only the formation of <jats:styled-content style="fixed-case">GC</jats:styled-content>‐like structures in <jats:styled-content style="fixed-case">NP</jats:styled-content> is described. The aim of this study was to investigate the involvement of local IgE production, class switch recombination, and receptor revision in <jats:styled-content style="fixed-case">NP</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compared the levels of local IgE, germline gene transcripts, and mature Ig <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression, recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation, and GC reactions in NP tissue <jats:italic>vs</jats: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).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats: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 <jats:styled-content style="fixed-case">mRNA</jats:styled-content> concentrations are increased in NP and correlated with the magnitude of inflammation and the presence of <jats:italic>S. aureus</jats:italic> enterotoxin (superantigen)‐specific IgE in the nasal polyp mucosa.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats: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 <jats:styled-content style="fixed-case">NP</jats:styled-content>.</jats:p></jats:sec>