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

P. Gevaert; K. T. Nouri-Aria; H. Wu; C. E. Harper; P. Takhar; D. J. Fear; F. Acke; N. De Ruyck; G. Banfield; H. H. Kariyawasam; C. Bachert; S. R. Durham; Hannah Gould

doi:10.1111/all.12054

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

P. Gevaert^*, K. T. Nouri-Aria, H. Wu, C. E. Harper, P. Takhar, D. J. Fear, F. Acke, N. De Ruyck, G. Banfield, H. H. Kariyawasam, C. Bachert, S. R. Durham, Hannah Gould

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

129 Citations (Scopus)

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.

Original language	English
Pages (from-to)	55-63
Number of pages	9
Journal	Allergy
Volume	68
Issue number	1
DOIs	https://doi.org/10.1111/all.12054
Publication status	Published - Jan 2013

Keywords

germinal center-like structures
HYPERMUTATION
DISEASES
ALLERGIC RHINITIS
TISSUE
IgE
TRANSCRIPTS
MUCOSA
receptor revision
B-CELL
RECOMBINATION
ORGANIZATION
nasal polyps
allergic rhinitis
EXPRESSION

Access to Document

10.1111/all.12054

Cite this

@article{ae8c47f98f91485abb795a19e986e2b5,

title = "Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps",

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 = "germinal center-like structures, HYPERMUTATION, DISEASES, ALLERGIC RHINITIS, TISSUE, IgE, TRANSCRIPTS, MUCOSA, receptor revision, B-CELL, RECOMBINATION, ORGANIZATION, nasal polyps, allergic rhinitis, EXPRESSION",

author = "P. Gevaert and Nouri-Aria, {K. T.} and H. Wu and Harper, {C. E.} and P. Takhar and Fear, {D. J.} and F. Acke and {De Ruyck}, N. and G. Banfield and Kariyawasam, {H. H.} and C. Bachert and Durham, {S. R.} and Hannah Gould",

year = "2013",

month = jan,

doi = "10.1111/all.12054",

language = "English",

volume = "68",

pages = "55--63",

journal = "Allergy",

issn = "0105-4538",

publisher = "Blackwell Publishing",

number = "1",

}

TY - JOUR

T1 - Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps

AU - Gevaert, P.

AU - Nouri-Aria, K. T.

AU - Wu, H.

AU - Harper, C. E.

AU - Takhar, P.

AU - Fear, D. J.

AU - Acke, F.

AU - De Ruyck, N.

AU - Banfield, G.

AU - Kariyawasam, H. H.

AU - Bachert, C.

AU - Durham, S. R.

AU - Gould, Hannah

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

KW - germinal center-like structures

KW - HYPERMUTATION

KW - DISEASES

KW - ALLERGIC RHINITIS

KW - TISSUE

KW - IgE

KW - TRANSCRIPTS

KW - MUCOSA

KW - receptor revision

KW - B-CELL

KW - RECOMBINATION

KW - ORGANIZATION

KW - nasal polyps

KW - allergic rhinitis

KW - EXPRESSION

U2 - 10.1111/all.12054

DO - 10.1111/all.12054

M3 - Article

SN - 0105-4538

VL - 68

SP - 55

EP - 63

JO - Allergy

JF - Allergy

IS - 1

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this