Synchronous immune alterations mirror clinical response during allergen immunotherapy - 04/05/18
Abstract |
Background |
Three years of treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) trial demonstrated that 2 years of treatment through either route was effective in suppressing the response to nasal allergen challenge, although it was insufficient for inhibition 1 year after discontinuation.
Objective |
We sought to examine in the GRASS trial the time course of immunologic changes during 2 years of sublingual and subcutaneous immunotherapy and for 1 year after treatment discontinuation.
Methods |
We performed multimodal immunomonitoring to assess allergen-specific CD4 T-cell properties in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-facilitated allergen binding).
Results |
All 3 of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years of allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunologic effect. Although frequencies of antigen-specific TH2 cells in peripheral blood determined by using HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE antibody–dependent functional assays remained inhibited in part 1 year after discontinuation.
Conclusion |
Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific TH2 cells most closely paralleled the transient clinical outcome, and it is likely that recurrence of the T-cell drivers of allergic immunity abrogated the potential for durable tolerance. On the other hand, the persistence of IgE blocking antibody 1 year after discontinuation might be an early indicator of a protolerogenic mechanism.
Le texte complet de cet article est disponible en PDF.Key words : Allergy, immunotherapy, immune tolerance, allergen desensitization, TH2 cells
Abbreviations used : CRTH2, FAB, GRASS, PE, PP
Plan
Research reported in this publication was sponsored by the Immune Tolerance Network and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) under award no. UM1AI109565 and NIH grant R01 AI095074. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. |
|
Disclosure of potential conflict of interest: A. Renand receives grant support from the National Institutes of Health (NIH). M. H. Shamji serves as a consultant for Imperial College London and receives lecture fees from ALK-Abelló, ASIT Biotech, Allergopharma, and UCB. K. M. Harris receives grant support from the National Institute of Allergy and Infectious Diseases (NIAID)/NIH. E. Wambre receives grant support from the Immune Tolerance Network and NIH and is an employee of Benaroya Research Institute. P. A. Wurtzen is an employee of ALK-Abelló and hold stocks with ALK-Abelló. S. J. Till serves as a consultant for ALK-Abelló and Aimmune and receives grant support from Astra Zeneca and ASIT Biotech. G. T. Nepom receives grant support from NIH. W. W. Kwok receives grant support from the NIH. S. R. Durham receives grant support from the Immune Tolerance Network, NIAID, ALK-Abelló, Hørsholm Regeneron, and Biotech Tools and serves as a consultant from Anergis, Circassia, Biomay, Merck, Allergy Therapeutics, Med Update GmbH, and Food Standards. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 5
P. 1750 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?