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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, B-9000 Ghent, Belgium. philippe.gevaert@UGent.be
authors.forename: P
authors.initials: P
authors.lastname: Gevaert
authors.forename: K T
authors.initials: KT
authors.lastname: Nouri-Aria
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: C E
authors.initials: CE
authors.lastname: Harper
authors.forename: P
authors.initials: P
authors.lastname: Takhar
authors.forename: D J
authors.initials: DJ
authors.lastname: Fear
authors.forename: F
authors.initials: F
authors.lastname: Acke
authors.forename: N
authors.initials: N
authors.lastname: De Ruyck
authors.forename: G
authors.initials: G
authors.lastname: Banfield
authors.forename: H H
authors.initials: HH
authors.lastname: Kariyawasam
authors.forename: C
authors.initials: C
authors.lastname: Bachert
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: H J
authors.initials: HJ
authors.lastname: Gould
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000209:etiology* / Q000473:pathology; D012220:Rhinitis / Q000209:etiology*; D012852:Sinusitis / Q000209:etiology*; D027041:Somatic Hypermutation, Immunoglobulin; D013211:Staphylococcus aureus / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D018398:Homeodomain Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D007073:Immunoglobulin E