Marta Ponce1, Fabian Schroeder2, Christina Bannert1, Klara Schmidthaler1, Christian Skjødt Hansen3, Katrine Lindholm Bøgh4, Regina Soldo2, Stephen Kwok-Wing Tsui5,6, Andreas Weinhäusel2, Zsolt Szépfalusi1, Thomas Eiwegger1,7,8,9. 1. Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. 2. Competence Unit for Molecular Diagnostics, AIT, Austrian Institute of Technology, Vienna, Austria. 3. Evaxion Biotech, Copenhagen, Denmark. 4. National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark. 5. Hong Kong Bioinformatics Centre, Chinese University of Hong Kong, Hong Kong, China. 6. School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China. 7. Program in Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. 8. Department of Immunology, The University of Toronto, Toronto, Ontario, Canada. 9. Division of Immunology and Allergy, Food allergy and Anaphylaxis Program, The Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract
BACKGROUND: The preventive effect of allergen immunotherapy (AIT) on allergy and asthma development is currently assessed using primary and secondary AIT approaches. Knowledge of the immunological effects of these interventions is limited and the impact on epitope diversity remains to be defined. METHODS: We used high-density peptide arrays that included all known Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) allergens and the whole proteome of Der f to study changes in House Dust Mite (HDM) linear peptide recognition during a 2-year preventive double-blind placebo-controlled sublingual HDM AIT pilot study in 2-5-year-old children with sensitization to HDM but without symptoms. RESULTS: Preventive AIT-treated patients showed significantly higher IgG epitope diversity to HDM allergens compared to placebo-treated individuals at 24 months of treatment (P < 0.05), while no increase in IgE diversity was seen. At 24 months of treatment, IgG4 diversity for HDM allergens was significantly higher in the pAIT-treated patients compared to placebo group (P < 0.05). Potentially beneficial changes in epitope recognition throughout the treatment are also seen in peptides derived from Der f proteome. CONCLUSION: These data suggest a beneficial immunomodulation of preventive sublingual immunotherapy at a molecular level by favoring a broader blocking repertoire and inhibiting epitope spreading.
RCT Entities:
BACKGROUND: The preventive effect of allergen immunotherapy (AIT) on allergy and asthma development is currently assessed using primary and secondary AIT approaches. Knowledge of the immunological effects of these interventions is limited and the impact on epitope diversity remains to be defined. METHODS: We used high-density peptide arrays that included all known Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) allergens and the whole proteome of Der f to study changes in House Dust Mite (HDM) linear peptide recognition during a 2-year preventive double-blind placebo-controlled sublingual HDM AIT pilot study in 2-5-year-old children with sensitization to HDM but without symptoms. RESULTS: Preventive AIT-treated patients showed significantly higher IgG epitope diversity to HDM allergens compared to placebo-treated individuals at 24 months of treatment (P < 0.05), while no increase in IgE diversity was seen. At 24 months of treatment, IgG4 diversity for HDM allergens was significantly higher in the pAIT-treated patients compared to placebo group (P < 0.05). Potentially beneficial changes in epitope recognition throughout the treatment are also seen in peptides derived from Der f proteome. CONCLUSION: These data suggest a beneficial immunomodulation of preventive sublingual immunotherapy at a molecular level by favoring a broader blocking repertoire and inhibiting epitope spreading.
Authors: Heimo Breiteneder; Zuzana Diamant; Thomas Eiwegger; Wytske J Fokkens; Claudia Traidl-Hoffmann; Kari Nadeau; Robyn E O'Hehir; Liam O'Mahony; Oliver Pfaar; Maria J Torres; De Yun Wang; Luo Zhang; Cezmi A Akdis Journal: Allergy Date: 2019-06-04 Impact factor: 13.146