Long-term clinical and immunological effects of allergen immunotherapy
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.
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ABSTRACT: Aluminum-containing adjuvants are widely used in preventive vaccines against infectious diseases and in preparations for allergy immunotherapy. The mechanism by which they enhance the immune response remains poorly understood. Aluminum adjuvants selectively stimulate a Th2 immune response upon injection of mice and a mixed response in human beings. They support activation of CD8 T cells, but these cells do not undergo terminal differentiation to cytotoxic T cells. Adsorption of antigens to aluminum adjuvants enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site which allows time for inflammatory cells to accumulate. The adsorptive strength is important as high affinity interactions interfere with the immune response. Adsorption can also affect the physical and chemical stability of antigens. Aluminum adjuvants activate dendritic cells via direct and indirect mechanisms. Phagocytosis of aluminum adjuvants followed by disruption of the phagolysosome activates NLRP3-inflammasomes resulting in the release of active IL-1β and IL-18. Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells. The use of aluminum adjuvant is limited by weak stimulation of cell-mediated immunity. This can be enhanced by addition of other immunomodulatory molecules. Adsorption of these molecules is determined by the same mechanisms that control adsorption of antigens and can affect the efficacy of such combination adjuvants. The widespread use of aluminum adjuvants can be attributed in part to the excellent safety record based on a 70-year history of use. They cause local inflammation at the injection site, but also reduce the severity of systemic and local reactions by binding biologically active molecules in vaccines.Frontiers in Immunology 01/2012; 3:406. DOI:10.3389/fimmu.2012.00406
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ABSTRACT: Subcutaneous immunotherapy (SCIT) is still questioned as a safe and efficacious way of treating allergic asthma in children. In a Cochrane review published in 2010 it was, however, concluded that SCIT has significant and beneficial effects on symptoms and medication use in both children and adults with mostly mild asthma. Only a few studies have been performed to specifically study if SCIT in children with moderate asthma reduces the need for inhaled corticosteroids. There are conflicting results that illustrate the problem of the heterogeneity of the asthma disease and the fact that allergies may play different roles on the severity and symptoms of the disease. Furthermore, children with severe allergic asthma are often sensitized to multiple allergens, which makes SCIT both complicated and less safe to administer. On the other hand, if the child suffers from asthmatic symptoms despite adherence to pharmacotherapy, omalizumab or a combination of omalizumab and allergen immunotherapy might be useful. There is a need for more studies on this combination before it can be considered as an additional therapy in children with asthma and severe allergies. Sublingual immunotherapy (SLIT) has also been shown to improve asthma symptoms and medication use. SLIT is safe although its efficacy compared with SCIT has been studied very little. Another approach is to try to prevent asthma by treating children with SCIT for allergic rhinoconjunctivitis before asthma has developed. The most attractive prospect, however, is to find ways of preventing asthma by vaccination against the most common viruses, particularly rhinovirus. There is evidence that there are children at high risk of developing asthma in whom a viral infection can also enhance the risk of allergen sensitization. So far this vaccination has not been achievable although research is in progress.Therapeutic Advances in Respiratory Disease 03/2012; 6(3):137-46. DOI:10.1177/1753465812439793 · 1.95 Impact Factor
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ABSTRACT: Background. Allergen-specific immunotherapy (SIT) is one of the important regimens for the treatment of allergic diseases. Predictive tests for the clinical response to SIT are limited. In this study we aimed to evaluate whether specific IgE/total IgE levels can predict clinical improvement in monosensitized patients to house dust mite treated with immunotherapy. Patients and Methods. We analyzed 32 patients who had undergone 2 years of SIT. Serum t-IgE and s-IgE levels, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to SIT. Asthma symptom score (ASS), rhinitis symptom score (RSS), pulmonary functions and visual analogue scales (VAS) were evaluated at the beginning and after 2 years. Results. There were 17 boys and 15 girls with the mean age of 10.78 ± 3.03 years. The mean serum house dust mite s-IgE level was 128.62 ± 142.61 kU/L, t-IgE 608.90 ± 529.98 IU/mL, and s-IgE/t-IgE ratio 33.83 ± 53.18. Before immunotherapy, ASS was 6.23 ± 1.63, RSS; 8.20 ± 1.88, VAS; 7.38 ± 2.01, FEV1 (%); 89.14 ± 8.48, PEF (%); 88.93 ± 13.57, and after 2 years, these values were determined as 1.90 ± 1.10, 3.05 ± 1.39, 1.35 ± 1.24, 97.6 ± 11.26, and 97.0 ± 11.55, respectively. s-IgE/t-IgE ratio was correlated with change in RSS (r = -0.392, P = 0.08) and VAS (r = -0.367, P = 0.05). Conclusion. Although SIT is very effective treatment, all patients do not benefit from treatment. We assumed that s-IgE/t-IgE ratio would be useful to predict the clinical response to SIT.Journal of Allergy 03/2012; 2012:694094. DOI:10.1155/2012/694094