The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias

• Published in: Journal of allergy and clinical immunology 2007-09, Vol.120 (3), p.696-706
• Main Authors: Lim, Annick, MSci, Luderschmidt, Stephan, MD, Weidinger, Anke, MD, Schnopp, Christina, MD, Ring, Johannes, MD, Hein, Rüdiger, MD, Ollert, Markus, MD, Mempel, Martin, MD
• Format: Article
• Language: English
• Subjects: Adult; Allergic diseases; Allergies; Allergy and Immunology; Anti-Allergic Agents - therapeutic use; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Asthma; atopic eczema; B cells; Biological and medical sciences; Cloning; Eczema; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Rearrangement, B-Lymphocyte - drug effects; Genes, Immunoglobulin; Humans; Hypersensitivity, Immediate - drug therapy; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - immunology; IgE repertoire; Immune system; Immunoglobulin E - drug effects; Immunoglobulin E - genetics; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin Heavy Chains - drug effects; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulin M - blood; Immunoglobulin Variable Region - drug effects; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - immunology; Immunopathology; Leukocytes, Mononuclear - immunology; Male; Medical sciences; Middle Aged; Omalizumab; Patients; Receptor-CD3 Complex, Antigen, T-Cell - drug effects; Receptor-CD3 Complex, Antigen, T-Cell - genetics; Receptor-CD3 Complex, Antigen, T-Cell - immunology; Reverse Transcriptase Polymerase Chain Reaction; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Transcription, Genetic
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.05.035

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. Objectives 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) ϵ 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. Conclusion 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. Clinical implications The detailed analysis of the IgE B-cell repertoire is highly suitable to follow changes in IgE uses during different therapy modalities.