Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success.

BACKGROUND: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. METHODS: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. RESULTS: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. CONCLUSIONS: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

Seasonal changes in antigen-specific T-helper clone sizes in patients with Japanese cedar pollinosis: a 2-year study.

BACKGROUND: Allergic rhinitis (AR) is a typical type I allergic disease that occurs through the induction of allergen-specific effector T cells. Once established, new effector T cells derive mostly from memory T cells that are capable of surviving for extended periods, although the mechanisms by which these memory functions are maintained have not yet been clarified. In particular, the exact life-span of memory T cells is still not well understood. OBJECTIVE: Pollinosis patients seemed to be suitable subjects to investigate because such patients are exposed to antigens strongly for only a limited period once a year. We compared the seasonal changes in memory T-helper type 2 (Th2) between pollinosis and perennial allergic subjects. METHODS: The clone sizes of the Japanese cedar pollen-specific memory Th cells were measured by an ELISPOT assay using specific peptides from the patients with cedar pollinosis, and the seasonal changes were noted. This study was performed for 2 years. The cedar-specific IgE levels in the peripheral blood were also studied. Mite allergy patients were also enrolled in the study. RESULTS: The Japanese cedar-specific IL-4-producing Th2 cells were detected in all patients examined, although the number of cells was low. These Th memory cells increased during the pollen season and decreased during the off-season. However, more than 60% of the cedar-specific memory Th2 cells survived up to 8 months after the pollen season. The cedar-specific IgE levels exhibited changes similar to the cedar-specific Th cells. On the other hand, there was no drifting of Th memory clone size with the mite allergics, and the IgE levels also did not change. CONCLUSIONS: While pollen-specific Th cells decreased after pollen exposure, their memory functions continued. Memory clone size maintenance therefore requires repetitive antigen irritation.