5 years ago

Synchronous Immune Alterations Mirror Clinical Response During Allergen Immunotherapy

Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. Objective To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation. Methods We performed multi-modal 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 three of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunological effect. Whereas frequencies of antigen-specific Th2 cells in peripheral blood determined by HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE-antibody dependent functional assays remained partially inhibited one year following 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, persistence of IgE-blocking antibody one year after discontinuation may be an early indicator of a pro-tolerogenic mechanism.

Publisher URL: www.sciencedirect.com/science

DOI: S0091674917317359

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