Stefania Zanotta

Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production

BACKGROUND Sublingual immunotherapy (SLIT) is safe and efficacious in the treatment of patients with allergic rhinitis. Although favorable clinical effects have been observed with controlled trials as early as a few months since the beginning of treatment, few biological changes induced by SLIT have been demonstrated. OBJECTIVE To investigate in grass-allergic patients the effect of a 2-month SLIT regimen, administered with a simplified protocol without up-dosing, on proliferation and production of cytokines characteristic of the regulatory T-cell phenotype (interleukin 10 [IL-10] and transforming growth factor beta [TGF-beta]) by allergen-specific T cells. METHODS Patients were recruited to the study in January 2006. SLIT was performed by self-administration and was continued for 60 days from February to April 2006. Eleven grass pollen-allergic patients with seasonal rhinitis were treated daily before the pollen season for 2 months with a modified allergen (monomeric allergoid) derived from a 3-grass pollen extract. Allergen-specific proliferation and production of IL-10 and TGF-beta were measured on peripheral blood mononuclear cells at baseline and treatment end. Tetanus toxoid served as the control antigen. RESULTS After SLIT, allergen-specific (P = .002) but not tetanus toxoid-specific proliferation decreased, whereas IL-10 transcription increased (P < .001). TGB-beta transcription was also increased after treatment, although not statistically significantly (P = .06). Changes in proliferation to allergen and in IL-10 transcription were correlated (r = -0.82, P = .003). CONCLUSIONS A short-term course of SLIT with modified allergen in grass-allergic patients is associated with the reduction of allergen-specific proliferation and with the up-regulation of the IL-10 regulatory cytokine.

Clinical and immunological correlates of pre-co-seasonal sublingual immunotherapy with birch monomeric allergoid in patients with allergic rhinoconjunctivitis.

Sublingual immunotherapy is safe and efficacious in the treatment of patients with allergic rhinitis. The clinical and biological efficacy of modified allergens (allergoids) has not been fully clarified. We investigated in birch allergic patients the effect of a pre-co-seasonal sublingual immunotherapy regimen with a modified allergen extract on clinical parameters and on T cell proliferation and regulatory cytokine production (IL-10, TGF-beta). We found that during the birch pollen season symptoms and drug usage scores were 30 and 40% improved, respectively, in treated versus control subjects (p<0.0001 for both comparisons) whereas well days were 23.5 (33%) versus 16.9 (23%) (p=0.0024), respectively. Bet v 1 allergen specific proliferation decreased (p = 0.0010), whereas IL-10 transcription increased (p = 0.0010) in treated, but not in control patients. Moreover, TGF-beta transcription was increased, although not significantly (p=0.066), following immunotherapy. Thus, sublingual immunotherapy with modified allergen in birch-allergic subjects was safe, clinically efficacious and associated with the reduction of allergen-specific proliferation and with the increased production of the IL-10 regulatory cytokine.

Vitamin D3 improves the effects of low dose Der p 2 allergoid treatment in Der p 2 sensitized BALB/c mice.

BackgroundAirborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition because it is able to modify its natural course by opposing the underlying pathogenic mechanisms and determining immune suppression, immune deviation and tolerance. The rational for the present study was to investigate the possibility of improving allergoid-based IT in terms of efficacy and safety. Recently, 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells and to be a good adjuvant in AIT settings.MethodsWe investigated whether the co-administration of VD3 could potentiate the effect of AIT even when added to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in a Derp p 2 (d2)-sensitized BALB/c mice model. Control groups where treated with sham, VD3 alone or d2-OID only.ResultsThe d2-OID alone was not fully successful, as expected for a low dose. VD3 administration was associated with some valuable, although limited, changes in the immunological parameters in the lung. On the contrary, the VD3 adjuvated allergoid vaccine induced the most prominent reduction of airway eosinophilia and Th2 cytokines and concomitant increase of T regulatory cells and IL-10 in the lung and Der p 2-specific IgG2a in the serum.ConclusionsThe addition of VD3 to a conventional AIT protocol would allow the reduction of allergoid dose needed and therefore, the production costs. Moreover, beneficial immunomodulatory effects have been achieved by the oral administration which might favour the management of the therapy by the patients and their adherence, possibly enhancing the efficacy of the treatment.

rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant

Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice.