Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 5; pp. 1153 - 1158.e2
• Main Authors: Novak, Natalija, Mete, Nihal, Bussmann, Caroline, Maintz, Laura, Bieber, Thomas, Akdis, Mübeccel, Zumkehr, Judith, Jutel, Marek, Akdis, Cezmi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2012; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Allergens; Allergies; Allergy and Immunology; Animals; basophils; Basophils - drug effects; Basophils - immunology; Bee Venoms - therapeutic use; Beekeeping; Bees; Biological and medical sciences; Cells, Cultured; Colleges & universities; Cytokines; Drugs; Enzyme-linked immunosorbent assay; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histamine; histamine receptor 2; Histamine receptors; Human; Humans; Hypersensitivity - immunology; Hypersensitivity - therapy; Immunoglobulin E; Immunological tolerance; Immunopathology; Immunosuppression; Immunotherapy; Insect Bites and Stings - immunology; Insect Bites and Stings - therapy; Kinases; Leukocytes (basophilic); Male; Mast cells; Medical sciences; Middle Aged; patients; Peripheral blood; Polymerase chain reaction; quantitative polymerase chain reaction; receptors; Receptors, Histamine H2 - metabolism; Receptors, IgE - antagonists & inhibitors; Receptors, IgE - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; tolerance; ultrarush immunotherapy; Venom; venoms; Venoms - therapeutic use; Wasp Venoms - urine; Young Adult; Germany; Human; VIT; histamine receptor 2; HR; basophils; cAMP; ultrarush immunotherapy; tolerance; SIT; Venom immunotherapy; Cyclic AMP; Allergen-specific immunotherapy; Histamine receptor; Immunopathology; Suppression; Granulocyte; Tolerance; Activation; Basophil; Histamine; Immunology; Treatment; Immunotherapy; Ultrarush desensitization; Early; Biological receptor
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.04.039

Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs). We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking–mediated basophil function and mediator release. Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays. Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro. Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.