Follicular T helper and Breg cell balance in severe allergic asthma before and after omalizumab therapy

Abstract

Background Severe allergic asthma (SAA) is based on type 2 (T2-high) immune responses to allergens promoting type 2 T helper (Th2) cell cytokine responses and production of IgE antibodies. Omalizumab was the first biological drug licensed for clinical use in the management of IgE-mediated SAA. Despite, emerging evidence supporting the prominent role of follicular T cells (Tfh), Breg and Treg subsets, in the development and progression of SAA, no data is available on the impact omalizumab therapy. Methods Ten SAA patients monitored at the Respiratory Diseases Unit of Siena University Hospital and 10 healthy sex- and age-matched controls were enrolled in the study. Clinical and functional parameters were collected at baseline (T0) and after 6 months of therapy (T6). Cellular population analysis were determined through multi-color flow cytometry. Results SAA patients showed higher percentages of Th17.1, Tfh and Tfh2 while CD24 hi CD27 hi Breg cell, Treg and Tfr percentages were significantly lower than controls. Higher percentages of Tfh2 in patients with nasal polyps than in those without and in controls were observed. At T6, significant decreases of Tfh and Tfh2 than T0 were observed. A slightly significant increase in Teff was reported at T6 with respect to T0. ΔIgE levels in serum were correlated with ΔCD19 + CD24 + CD27 + Breg cell percentages (r=-0.86, p=0.0022). Conclusions Our data explored the changes of Tfh cells, Tregs and Bregs in severe asthma. The restoration of immunological imbalance in SAA patients after omalizumab is surely intriguing and represents a glimpse of light in the comprehension of immunological effects of treatment.