title: Prolonged Treatment of Peanut-Allergic Mice with Bortezomib Significantly Reduces Serum Anti-Peanut IgE but Does Not Affect Allergic Symptoms.
abstract: BACKGROUND
  Anti-peanut immunoglobulin E (anti-Pn IgE) can persist throughout life, suggesting that this condition could be maintained by long-lived antibody-secreting cells (ASCs). To determine the role of long-lived ASCs, peanut-allergic mice underwent prolonged treatment with the proteasome inhibitor, bortezomib (Bz).
  
  
  METHODS
  Intravenous Bz was given twice weekly for 21 weeks to peanut-allergic mice. During treatment, serum anti-Pn IgE was measured, and the mice were rechallenged at the end of treatment. Cell populations were measured, and Pn-specific IgG, total IgG, and total IgE ASCs were enumerated in the bone marrow (BM) and spleen (SPL).
  
  
  RESULTS
  Prolonged treatment with Bz significantly reduced serum anti-Pn IgE and IgG1 but did not affect symptoms following challenge with Pn, even in mice with undetectable serum anti-Pn IgE. Numbers of CD138+ cells were significantly reduced in the BM but were unaffected in the SPL. Unexpectedly, Bz did not affect numbers of Pn-specific IgG, total IgG, or total IgE ASCs in either the BM or SPL.
  
  
  CONCLUSIONS
  Cells that maintain long-lived serum anti-Pn IgE are sensitive to Bz. However, prolonged depletion of serum Pn-specific IgE does not result in a decrease of symptoms following challenge with Pn.
authors.affiliation: Division of Allergy and Clinical Immunology and Departments of Medicine and Immunology, University of Colorado Denver, Aurora, Colo., USA.
authors.forename: Daphne M
authors.initials: DM
authors.lastname: Moutsoglou
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Dreskin
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D010367:Arachis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D000069286:Bortezomib / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D021183:Peanut Hypersensitivity / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D010641:Phenotype
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D000069286:Bortezomib