title: Allergen immunotherapy:  a history of the first 100 years.
abstract: OBJECTIVE
  To provide a historical perspective on the development of allergen immunotherapy and to describe the progress that has been made in both the clinical application and the scientific understanding of this therapeutic technique in the 100 years since its inception.
  
  
  RESULTS
  Although allergen immunotherapy has been part of allergy practice for a century, it is only in relatively recent years that the cellular and molecular mechanisms which underlie its clinical efficacy have been elucidated. Most recent studies implicate the T-regulatory cell response as central to the development of a tolerogenic state in response to allergen immunotherapy, with both IL-10 and TGF-β playing crucial roles in the development of this cell subset. The clinical application of immunotherapy continues to advance, with promising contemporary studies noting improved safety and efficacy with pretreatment using omalizumab prior to an immunotherapy program as well as the potential for innate immune system modulation with allergen conjugates which can stimulate pattern recognition receptors such as the toll-like receptors.
  
  
  CONCLUSIONS
  After 100 years of clinical application, allergen immunotherapy remains the only treatment modality with the potential for long-term immunologic amelioration of atopic diseases. Future treatment advances in allergen immunotherapy will likely harness the increasing power of molecular and genomic medicine to achieve greater allergen specificity, while improving overall efficacy and minimizing the potential for systemic reactions.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA. dfitzhug@health.usf.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Fitzhugh
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
mesh_terms: D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003888:Desensitization, Immunologic / Q000266:history* / Q000639:trends; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D000069444:Omalizumab; D051192:Receptors, Pattern Recognition / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D051192:Receptors, Pattern Recognition; D000069444:Omalizumab