Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-γ- and interleukin-10-production

• Published in: Clinical and experimental allergy 2006-03, Vol.36 (3), p.261-272
• Main Authors: Cosmi, L., Santarlasci, V., Angeli, R., Liotta, F., Maggi, L., Frosali, F., Rossi, O., Falagiani, P., Riva, G., Romagnani, S., Annunziato, F., Maggi, E.
• Format: Article
• Language: English
• Subjects: Administration, Sublingual; Adolescent; Adult; Allergens - immunology; Allergic diseases; allergic rhinitis and asthma; Antigens, Dermatophagoides - immunology; Arthropod Proteins; Asthma - immunology; Asthma - therapy; Biological and medical sciences; Cell Proliferation; Cells, Cultured; Cysteine Endopeptidases; cytokines; Der p 1 allergen; Dermatophagoides pteronyssinus; Dermatophagoides pteronyssinus - immunology; Desensitization, Immunologic - methods; Down-Regulation - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE and IgG Abs; Immunoglobulin E - biosynthesis; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunopathology; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Male; Medical sciences; monomeric allergoid; Plant Extracts - immunology; Plant Extracts - therapeutic use; Rhinitis, Allergic, Perennial - immunology; Rhinitis, Allergic, Perennial - therapy; Severity of Illness Index; sublingual immunotherapy; symptom medication score; T cell proliferation; Th1; Th1 Cells - immunology; Th2 and Treg cell subsets; Th2 Cells - immunology; Treatment Outcome
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02429.x

Summary Background The clinical efficacy and safety of sublingual immunotherapy (SLIT) for aeroallergens has been demonstrated in several trials, whereas the immunological changes induced by this treatment, which may account for the clinical improvement, are still unclear. Objective To investigate the effects of a successful SLIT on the in vitro allergen‐driven T cell response and cytokine secretion as well as on the serum levels of chemokines and of IgE, IgG1 and IgG4 antibodies (Abs). Materials and methods Twenty‐five Dermatophagoides pteronyssinus (Dp)‐sensitive patients with perennial rhinitic and/or rhinitic and asthmatic symptoms were randomized into two groups (13 untreated (UT) and 12 SLIT‐treated) for a 1 year and half study. The proliferative response of peripheral blood mononuclear cell (PBMC) to purified Der p1 allergen, their cytokines (IFN‐γ, IL‐4, IL‐10 and TGF‐β) production and serum levels of chemokines associated with T helper type 1 (Th1) (CXCL10) or T helper type 2 (Th2) (CCL22) responses and of Dp‐specific IgE, IgG1 and IgG4 Abs were evaluated before and after 6 months of treatment. Results SLIT induced a significant reduction of symptom medication scores after 6, 12 and 18 months of treatment in comparison with UT patients. SLIT‐treated patients showed a significant decrease in serum levels of DP‐specific IgE Abs, whereas total IgE, and specific IgG1 and IgG4 Abs remained unchanged. The proliferative response of allergen‐specific T cells to Der p1 in vitro after 6 months of treatment was reduced, while no effect was observed on T cell proliferation to recall antigen (streptokinase). Moreover, Der p1‐driven IFN‐γ and IL‐10 were significantly increased in culture supernatants of PBMC from 6 month‐treated patients in comparison with those detected at the beginning of therapy. Conclusions These data suggest that the allergen‐driven enhancement of IL‐10‐ and IFN‐γ‐producing T cells precedes and associates with SLIT‐induced down‐regulation of specific IgE, thus providing a rationale to explain the clinical benefit of SLIT in allergic patients.