期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 141, 期 5, 页码 1750-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2017.09.041
关键词
Allergy; immunotherapy; immune tolerance; allergen desensitization; T(H)2 cells
资金
- Immune Tolerance Network
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) [UM1AI109565]
- NIH [R01 AI095074]
- MRC [G0601303] Funding Source: UKRI
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-acilitated 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 T(H)2 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-pecific T(H)2 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.
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