Clinical efficacy of sublingual and subcutaneous birch pollen allergen‐specific immunotherapy: a randomized, placebo‐controlled, double‐blind, double‐dummy study

Khinchi, Marianne Søndergaard; Poulsen, Lars K.; Carat, F.; André, C.; Hansen, Alastair; Malling, H.V.

doi:10.1046/j.1398-9995.2003.00387.x

Cited by 315 publications

(265 citation statements)

References 47 publications

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“…Only five trials have assessed this question. [32][33][34][35][36] Three of them have been performed with pollen allergens. 32,34,35 All of them are of weak methodology and all but one demonstrated a similar efficacy of the two routes of administration.…”

Section: Special Focus Reviewmentioning

confidence: 99%

Specific immunotherapy in grass pollen allergy

Mailhol

Didier²

2012

Human Vaccines & Immunotherapeutics

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Section: Special Focus Reviewmentioning

confidence: 99%

Specific immunotherapy in grass pollen allergy

Mailhol

Didier²

2012

Human Vaccines & Immunotherapeutics

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“…This suggests that tolerance induction might be a more desirable approach to therapy in allergic disease than immune deviation. Allergen-specific immunotherapy as a tolerization approach to management of atopic diseases can have clinical efficacy, but it is a cumbersome approach that can call for years of treatment to achieve high levels of efficacy (51,52). Should dendritic cell-based therapy for asthma eventually prove clinically useful, as proposed by others (16,53), its delivery may prove technically cumbersome, but therapeutically more satisfying in terms of both time to successful outcome and the depth of effect.…”

Section: Figure 5 Cd8␣mentioning

confidence: 99%

CD8α+, but Not CD8α−, Dendritic Cells Tolerize Th2 Responses via Contact-Dependent and -Independent Mechanisms, and Reverse Airway Hyperresponsiveness, Th2, and Eosinophil Responses in a Mouse Model of Asthma

Gordon

Nayyar

et al. 2005

The Journal of Immunology

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Splenic CD8α+ dendritic cells reportedly tolerize T cell responses by inducing Fas ligand-mediated apoptosis, suppressing IL-2 expression, or catabolizing T cell tryptophan reserves through expression of IDO. We report in this study that CD8α+, but not CD8α−, dendritic cells purified from the spleens of normal mice can tolerize the Th2 responses of cells from asthma phenotype mice through more than one mechanism. This tolerance could largely be reversed in vitro by anti-IL-10 or anti-TGFβ Ab treatment. However, loss of direct dendritic cell-T cell contact also reduced tolerance, although to a lesser extent, as did adding the IDO inhibitor 1-methyltryptophan or an excess of free tryptophan to the cultures. Within 3 wk of reconstituting asthma phenotype mice with 1 × 105 OVA-pulsed CD8α+, but not CD8α−, dendritic cells, the mice experienced a reversal of airway hyperresponsiveness, eosinophilic airway responses, and pulmonary Th2 cytokine expression. This data indicates that CD8α+ dendritic cells can simultaneously use multiple mechanisms for tolerization of T cells and that, in vivo, they are capable of tolerizing a well-established disease complex such as allergic lung disease/asthma.

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“…The higher amount of recombinant allergen needed to reproduce the typical symptoms of OAS, when compared with SPTs and nasal challenges, leads us to define that the oral mucosa has a higher threshold response than skin and nasal mucosa. Moreover, we should consider that the concentration of commercial extracts (100 IR) had an amount of natural major allergen lower than 50 mcglml (26,27) and that the negativity of oral challenges was probably due to the insufficient amount of natural allergen, lower than the oral threshold response. These low concentrations : may also be secondary to the demonstrated degradation of allergens during the preparation of commercial extracts (28).…”

Section: Discussionmentioning

confidence: 99%

Sublingual Reactivity to rBET V1 and rPHL P1 in Patients with Oral Allergy Syndrome

Marcucci

Sensi

Cara

et al. 2006

Int J Immunopathol Pharmacol

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Oral Allergy Syndrome (OAS) in patients with pollen-induced rhinoconjunctivitis is caused by specific IgE recognizing cross-reacting epitopes of fruits and plants, which were clearly shown in vitro, but failed to be demonstrated in vivo by cross-challenges in the target organs. Considering the hypothesis of degradation of such epitopes in natural extracts, challenges with recombinant pollen allergens were done to evaluate the reactivity of the oral mucosa in OAS patients. Seventeen patients with OAS and rhinitis from birch (10) and grass pollen (7) and 10 non-atopic controls were studied by skin prick tests (SPT), allergen specific nasal challenges (ASNC) and allergen specific sublingual challenges (ASSC) with birch and timothy extracts and with rBet vl and rPhl pt at increasing concentrations from 1 to 1000 meg/mi. None of the healthy subjects in the control group had any positive test for birch and timothy extracts or for recombinant allergens. In the OAS group the following results were observed: SPTs with recombinant allergens were positive in all patients, mostly at 10 mcg/ml concentration; ASNC with rBet vl were positive in all patients, mostly at 100 mcg/ml; ASSC with natural pollen extracts were positive in only 2 of 17 patients, but in 15 of'17 with rBet vl and rPhl pt, mostly at 500 mcg/ml and 1000 meg/mi. ASSC with rBet vi and rPhl p l were positive with a mean concentration of 677 and 533 mcg/ml, respectively. The results of sublingual challenges with rBet vl and rPhl pt showed the in vivo cross-reactivity between pollens and foods in patients with OAS, but high concentrations ofthe recombinant allergens were needed to reproduce oral symptoms, thus explaining the failure of challenges performed with natural extracts, which have concentrations of major allergens lower than 50 meg/mi. This indicates that sublingual mucosa is much less reactive to allergens than other surfaces, such as skin and nasal mucosa, probably because of its anatomic and immunologic peculiarity.Oral allergy syndrome (OAS) is a condition characterized by oral swelling and itching after the contact of specific foods with the oral mucosa (1). In most cases this syndrome occurs in patients with pollen-induced rhinoconjunctivitis when eating fresh fruits or vegetables (2-4). The etiology ofOAS is generally attributed to cross-reactivity between some food allergens and some inhalant allergens. The contact with the inhaled allergen leads to sensitization of upper and lower airways, with a production of specific IgE cross-reactive to food allergens, which, in turn, are responsible for the oral

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Clinical efficacy of sublingual and subcutaneous birch pollen allergen‐specific immunotherapy: a randomized, placebo‐controlled, double‐blind, double‐dummy study

Cited by 315 publications

References 47 publications

Specific immunotherapy in grass pollen allergy

Specific immunotherapy in grass pollen allergy

CD8α+, but Not CD8α−, Dendritic Cells Tolerize Th2 Responses via Contact-Dependent and -Independent Mechanisms, and Reverse Airway Hyperresponsiveness, Th2, and Eosinophil Responses in a Mouse Model of Asthma

Sublingual Reactivity to rBET V1 and rPHL P1 in Patients with Oral Allergy Syndrome

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