ZAP70 expression in regulatory T cells in allergic rhinitis: effect of immunotherapy.

BACKGROUND: Some allergic diseases may be accompanied by inappropriate number or malfunction of regulatory T cells, which seems to be modified by specific immunotherapy (SIT). OBJECTIVES: To assess if immunotherapy affects regulatory T lymphocytes (Tregs) and their expression of zeta chain associated protein kinase (Zap70), which is essential for T cell activation and intracellular signal downstream transduction. METHODS: A 3-year prospective, placebo-controlled, double-blind trial of grass SIT was conducted. Forty-one patients sensitized to grass pollen with intermittent allergic rhinitis were randomized to receive SIT (n = 21) or placebo (n = 20) and 15 healthy were included as a control. Concentration of exhaled nitric oxide (ENO), lung function, symptom scores, the subsets of regulatory T cells (CD4(+)  CD25hiCD127low) which express ZAP70 and the level of ZAP70 expression in this subset were assessed at baseline and during the treatment period: before the onset, at the height of the pollen season and after the end of the pollen season. RESULTS: The concentration of nitric oxide and the symptom score were significantly higher in allergic rhinitis patients as compared with the control group. Natural allergen stimulation diminished both the numbers of regulatory T cells that express ZAP70 and the expression of Zap70 within these cells. In the second year of treatment, immunotherapy reduced significantly the symptom scores, concentrations of ENO (P < 0.01), intensively increased expression of ZAP70 in regulatory T cells (P < 0.001) and the percentage of cells that express ZAP70 (P < 0.05) at the height of the pollen season. Placebo treatment did not reduce scores, ENO (P > 0.05) nor had influence on Zap70 expression (P > 0.05). CONCLUSIONS: SIT with grass pollen effectively reduces rhinitis severity and affects allergic airway inflammation reflected by reduction of ENO. Beneficial role of immunotherapy may result not only from the induction of Treg numbers but especially from cell activation and restitution of Treg intracellular signal transduction.

Quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine.

BACKGROUND: Persistent allergic rhinitis often impairs quality of life. OBJECTIVE: We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life. METHODS: A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed. RESULTS: In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39). CONCLUSIONS: Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.