title: The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias.
abstract: BACKGROUND
  Patients with atopic diseases are characterized by high levels of specific IgE production. However, little is known about the composition of their B-cell repertoires.
  
  
  OBJECTIVE
  We sought to analyze the complete PBMC-derived IgE repertoire and to compare clonal expansions between different patients.
  
  
  METHODS
  We have analyzed the IgE-bearing B-cell receptor repertoire in highly atopic patients (>1000 IU/mL) using quantitative RT-PCR, complementarity determining region 3 spectratyping, and sequence analysis. Three representative patients were additionally followed during anti-IgE therapy.
  
  
  RESULTS
  Atopic patients exhibited 100 to 1000 times more IgE-specific transcripts than control individuals. These patients used a variable region of the heavy immunoglobulin chain (VH) epsilon repertoire highly similar to their IgM and IgG repertoires, with preference of VH3b, VH4, VH3a, and VH1 segments. Each patient harbored individual clonal expansions, most probably as correlation of allergen-specific IgE production. Common expansions within the complementary determining region 3 shared by several individuals with similar sensitization patterns were found in spectratyping analysis. However, these antigen-driven expansions showed differences on the sequence level. In omalizumab-treated patients the clinical improvement was paralleled by a clear increase in the ratio of IgG/IgE transcripts.
  
  
  CONCLUSIONS
  The IgE repertoire in atopic patients follows the VH use patterns seen for other immunoglobulins and seems to preferentially recruit individual rearrangements rather than public expansions.
  
  
  CONCLUSIONS
  The detailed analysis of the IgE B-cell repertoire is highly suitable to follow changes in IgE uses during different therapy modalities.
authors.affiliation: Unité de Recherche et d'Expertise Immunité anti-virale, Biothérapie et Vaccins, Paris, France; INSERM U668, Institut Pasteur, Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.forename: Stephan
authors.initials: S
authors.lastname: Luderschmidt
authors.forename: Anke
authors.initials: A
authors.lastname: Weidinger
authors.forename: Christina
authors.initials: C
authors.lastname: Schnopp
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hein
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
mesh_terms: D000328:Adult; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000187:drug effects; D005803:Genes, Immunoglobulin; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007143:Immunoglobulin Heavy Chains / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood; D007135:Immunoglobulin Variable Region / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D000069444:Omalizumab; D007073:Immunoglobulin E