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J Allergy Clin Immunol. 2018 May;141(5):1750-1760.e1. doi: 10.1016/j.jaci.2017.09.041. Epub 2017 Nov 9.

Synchronous immune alterations mirror clinical response during allergen immunotherapy.

Author information

1
Benaroya Research Institute at Virginia Mason, Seattle, Wash.
2
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Section of Inflammation Repair and Development, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC and Asthma UK, Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
3
Immune Tolerance Network, Bethesda, Md.
4
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Section of Inflammation Repair and Development, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
5
Immunology, ALK-Abelló, Hørsholm, Denmark.
6
Asthma, Allergy and Lung Biology, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom; MRC and Asthma UK, Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
7
National Institute of Allergy and Infectious Diseases, Bethesda, Md.
8
Benaroya Research Institute at Virginia Mason, Seattle, Wash; Immune Tolerance Network, Bethesda, Md.
9
Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Section of Inflammation Repair and Development, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC and Asthma UK, Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: s.durham@imperial.ac.uk.

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.

KEYWORDS:

Allergy; T(H)2 cells; allergen desensitization; immune tolerance; immunotherapy

PMID:
29128670
PMCID:
PMC5938141
[Available on 2019-05-01]
DOI:
10.1016/j.jaci.2017.09.041
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