Abstract
BACKGROUND: In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T-cell response, which was preceded by an early decrease in the frequency of both IL-4+ cells and sIgE levels. A progressive increase in sIgG(4) levels and FAB blockage were also found. METHODS: By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow-up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy. RESULTS: Thirty patients completed the 5-year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL-4+ cells compared to the initial 1- to 4-month peak was maintained throughout the 3-year treatment period and for 2 years after discontinuation. Meanwhile, after a 2-year increase in sIgG4, the levels were stabilized during the third year and decreased post-therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T-cell response, after IT cessation, occurs in two-thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response. CONCLUSION: Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3-year treatment period) are linked to the acquisition and maintenance of a regulatory T-cell response.