title: Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs.
  
  
  OBJECTIVE
  We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions.
  
  
  METHODS
  Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with "matched" heavy and light chains were cloned as IgG1, and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays.
  
  
  RESULTS
  Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE.
  
  
  CONCLUSIONS
  SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as "superantibodies" through CDRs and framework regions to SEEs in SEE-anti-SEE IgE-FcεRI complexes.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jiun-Bo
authors.initials: JB
authors.lastname: Chen
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Louisa K
authors.initials: LK
authors.lastname: James
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Davies
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Yu-Chang Bryan
authors.initials: YB
authors.lastname: Wu
authors.affiliation: Allergy and Rhinology, Royal National Throat Nose Ear Hospital, London, United Kingdom.
authors.forename: Joanne
authors.initials: J
authors.lastname: Rimmer
authors.affiliation: Allergy and Rhinology, Royal National Throat Nose Ear Hospital, London, United Kingdom.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Lund
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jou-Han
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: McDonnell
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.
authors.forename: George H
authors.initials: GH
authors.lastname: Hutchins
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Tse Wen
authors.initials: TW
authors.lastname: Chang
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sutton
authors.affiliation: Allergy and Rhinology, Royal National Throat Nose Ear Hospital, London, United Kingdom.
authors.forename: Harsha H
authors.initials: HH
authors.lastname: Kariyawasam
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom; MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Campus, London, United Kingdom. Electronic address: hannah.gould@kcl.ac.uk.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
mesh_terms: D055963:Asthma, Aspirin-Induced / Q000276:immunology; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology; D002469:Cell Separation; D002908:Chronic Disease; D022801:Complementarity Determining Regions; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D020349:Surface Plasmon Resonance
chemical_list: D022801:Complementarity Determining Regions; D004768:Enterotoxins; D007074:Immunoglobulin G; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal; C019368:enterotoxin D, Staphylococcal; C026066:enterotoxin A, Staphylococcal; D007073:Immunoglobulin E
keywords: Chronic rhinosinusitis with nasal polyps; Staphylococcus aureus enterotoxin; aspirin-exacerbated respiratory disease; basophil; superantibody; superantigen