Basophil sensitivity reflects long-term clinical outcome of subcutaneous immunotherapy in grass pollen-allergic patients

Background: Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance. Objective: To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue. Methods: Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n = 18) or to an open control group (n = 6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3 months for three years treatment and every 6 months in the follow-up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment. Results: Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3 year-treatment period and 10-fold lower during the follow-up year (n = 18, P =.03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (ῥ=−0.69, P =.0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (ῥ = 0.63, P =.0012) and SPT (ῥ = 0.45, P =.03). Plasma cell numbers in the nasal mucosa increased during treatment (P =.02). Conclusion: Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment

Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and clinical benefit

© 2018 The Authors.[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 sIgG4 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.This work was supported by Genoma España and ALK‐Abello A/S