Article

Long-term clinical and immunological effects of allergen immunotherapy

Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
Current Opinion in Allergy and Clinical Immunology (Impact Factor: 3.66). 12/2011; 11(6):586-93. DOI: 10.1097/ACI.0b013e32834cb994
Source: PubMed

ABSTRACT The present review updates current findings on long-term clinical and immunological outcomes after cessation of allergen immunotherapy for allergic respiratory disease.
Recent studies have shown that allergen immunotherapy has sustained disease-modifying effects that persist for years after discontinuation. This is in contrast to the effects of antiallergic drugs that do not induce tolerance to offending allergens. Long-term effects of immunotherapy include a reduction in nasal symptoms, a decrease in the use of rescue medication and improvement in quality of life. These benefits are accompanied by immunological changes such as the induction of allergen-specific IgG antibodies with inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. One study reported a reduction in the development of asthma in children with seasonal pollen-induced rhinitis.
Allergen immunotherapy induces clinical and immunological tolerance as defined by persistence of clinical benefit and associated long-term immunological parameters after discontinuation of treatment. These findings are largely confined to studies of subcutaneous and sublingual immunotherapy for seasonal pollinosis. Further studies are needed to address potential long-term clinical effects for other seasonal and perennial inhaled allergens in both children and adults, and to identify potential biomarkers of tolerance.

1 Follower
 · 
173 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Allergen immunotherapy is a disease-modifying therapy, effective for the treatment of allergic rhinitis, allergic asthma, conjunctivitis or stinging insect allergy. Allergen immunotherapy involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response. Although precise underlying mechanisms of the induction of immune tolerance remain unclear, immunotherapy has been associated with the induction of distinct subsets of Tregs that eventually lead to peripheral tolerance by inducing a deviation from Th2 to Th1 immune responses. This review focuses on the current knowledge of the mechanisms of immunotherapy in relationship to different routes of administration and also provides a unifying view.
    Immunotherapy 06/2014; 6(6):775-86. DOI:10.2217/imt.14.47 · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulatory T cells play a critical role in the immune response to vaccination, but there is only a limited understanding of the response of regulatory T cells to aluminum adjuvants and the vaccines that contain them. Available studies in animal models show that although induced T regulatory cells may be induced concomitantly with effector T cells following aluminum-adjuvanted vaccination, they are unable to protect against sensitization, suggesting that under the Th2 immune-stimulating effects of aluminum adjuvants, Treg cells may be functionally compromised. Allergic diseases are characterized by immune dysregulation, with increases in IL-4 and IL-6, both of which exert negative effects on Treg function. For individuals with a genetic predisposition, the beneficial influence of adjuvants on immune responsiveness may be accompanied by immune dysregulation, leading to allergic diseases. This review examines aspects of the regulatory T cell response to aluminum-adjuvanted immunization and possible genetic susceptibility factors related to that response.
    Vaccine 07/2014; 32(40). DOI:10.1016/j.vaccine.2014.07.052 · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.Methods We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63+ CD193+SSLow basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with 2-2.5-fold increasing allergen doses in 10 steps starting at 1/1,000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 minutes of allergen stimulation (n=7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n=10).ResultsDesensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, p<0.0001). CD63 MFI expression was reduced from 68,248 (29,336-92,001) to 30,496 (14,046-46,179, p<0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen, resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, p=0.16 compared to grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, p=0.047) and correlated with decrease in CD63 upregulation (n=7, r>0.79, p<0.05).Conclusion Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation.This article is protected by copyright. All rights reserved.
    Allergy 07/2014; 69(10). DOI:10.1111/all.12482 · 6.00 Impact Factor