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Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps

(2013) ALLERGY. 68(1). p.55-63
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Abstract
BACKGROUND: 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. METHODS: 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 vs 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). RESULTS: 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 S. aureus enterotoxin (superantigen)-specific IgE in the nasal polyp mucosa. CONCLUSION: 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.
Keywords
allergic rhinitis, IgE, germinal center-like structures, nasal polyps, receptor revision, ALLERGIC RHINITIS, B-CELL, RECOMBINATION, EXPRESSION, MUCOSA, TISSUE, TRANSCRIPTS, HYPERMUTATION, ORGANIZATION, DISEASES

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MLA
Gevaert, Philippe, et al. “Local Receptor Revision and Class Switching to IgE in Chronic Rhinosinusitis with Nasal Polyps.” ALLERGY, vol. 68, no. 1, 2013, pp. 55–63, doi:10.1111/all.12054.
APA
Gevaert, P., Nouri-Aria, K. T., Wu, H., Harper, C. E., Takhar, P., Fear, D. J., … Gould, H. J. (2013). Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. ALLERGY, 68(1), 55–63. https://doi.org/10.1111/all.12054
Chicago author-date
Gevaert, Philippe, Kayhan T Nouri-Aria, HuiFen Wu, Claire E Harper, Pooja Takhar, David J Fear, Frederic Acke, et al. 2013. “Local Receptor Revision and Class Switching to IgE in Chronic Rhinosinusitis with Nasal Polyps.” ALLERGY 68 (1): 55–63. https://doi.org/10.1111/all.12054.
Chicago author-date (all authors)
Gevaert, Philippe, Kayhan T Nouri-Aria, HuiFen Wu, Claire E Harper, Pooja Takhar, David J Fear, Frederic Acke, Natalie De Ruyck, Graham Banfield, Harsha H Kariyawasam, Claus Bachert, Stephen R Durham, and Hannah J Gould. 2013. “Local Receptor Revision and Class Switching to IgE in Chronic Rhinosinusitis with Nasal Polyps.” ALLERGY 68 (1): 55–63. doi:10.1111/all.12054.
Vancouver
1.
Gevaert P, Nouri-Aria KT, Wu H, Harper CE, Takhar P, Fear DJ, et al. Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. ALLERGY. 2013;68(1):55–63.
IEEE
[1]
P. Gevaert et al., “Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps,” ALLERGY, vol. 68, no. 1, pp. 55–63, 2013.
@article{3111711,
  abstract     = {{BACKGROUND: 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.
METHODS: 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 vs 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).
RESULTS: 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 S. aureus enterotoxin (superantigen)-specific IgE in the nasal polyp mucosa. 
CONCLUSION: 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.}},
  author       = {{Gevaert, Philippe and Nouri-Aria, Kayhan T and Wu, HuiFen and Harper, Claire E and Takhar, Pooja and Fear, David J and Acke, Frederic and De Ruyck, Natalie and Banfield, Graham and Kariyawasam, Harsha H and Bachert, Claus and Durham, Stephen R and Gould, Hannah J}},
  issn         = {{1398-9995}},
  journal      = {{ALLERGY}},
  keywords     = {{allergic rhinitis,IgE,germinal center-like structures,nasal polyps,receptor revision,ALLERGIC RHINITIS,B-CELL,RECOMBINATION,EXPRESSION,MUCOSA,TISSUE,TRANSCRIPTS,HYPERMUTATION,ORGANIZATION,DISEASES}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{55--63}},
  title        = {{Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps}},
  url          = {{http://doi.org/10.1111/all.12054}},
  volume       = {{68}},
  year         = {{2013}},
}

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