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.
"One case displayed a systemic adverse reaction and the remaining cases showed local adverse reactions. Similar to previous studies (17,18), the local adverse reactions in the present study were manifested as local induration, induced cough and urticaria. The rate of adverse reactions was 11.7%. "
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to evaluate the efficacy of three-year subcutaneous SQ-standardized specific immunotherapy (SCIT) in house dust mite (HDM)-allergic children with asthma. Ninety children with allergic asthma to HDMs, with or without allergic rhinitis, were randomly divided into two groups, the treatment group and the control group. The treatment group received SCIT combined with standardized glucocorticoid management and the control group received standardized glucocorticoid management alone for a period of three years. The mean daily dose of inhaled corticosteroids (ICSs), a four-week diary recording the symptom scores of asthma, peak expiratory flow (PEF) measurements, skin prick test results and serum immunoglobulin E (IgE) levels were assessed prior to treatment and following one, two and three years of treatment. The median dose of ICS was reduced in the treatment group after two and three years of treatment compared with that of the control group. After three years of treatment, the discontinuation percentage of ICS in the treatment group was higher than that in the control group. The treatment group demonstrated significantly reduced daytime and night-time asthmatic symptom scores, increased PEF values and reduced serum IgE levels after two and three years of treatment compared with those in the control group (P<0.05). In conclusion, three-year SCIT treatment combined with ICS is an effective immunotherapy for children with allergic asthma and resulted in a reduction of the required ICS dose.
Experimental and therapeutic medicine 03/2014; 7(3):630-634. DOI:10.3892/etm.2014.1469 · 1.27 Impact Factor
"Even after end of treatment period, immunotherapy provides persistent effects of long-term reduced symptoms/ need for medication as well as long-term reduced hyperresponsiveness and late phase response . Immunotherapy also provides preventive effect: it seems not only to reduce the development of new allergic sensitivities as measured by skin prick test or allergen-specific IgE but also to provide preventive effect on later development of asthma in children with seasonal rhinoconjunctivitis [6, 7]. "
[Show abstract][Hide abstract] ABSTRACT: Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far.
We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule.
To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times.
Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR.
This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.
"With a prevalence of up to 30% in developed countries, IgE-mediated allergic diseases have become a major burden for public health systems 1. Introduced 100 years ago 2–4, specific immunotherapy (SIT) still is the only causal treatment for patients suffering from rhinoconjunctivitis, asthma, or hypersensitivity to insect venom, by redirecting inappropriate T helper 2 (Th2)-driven immune responses against allergens. Despite its proven clinical efficacy 5,6, only a small percentage of allergic patients decide to undergo SIT instead of symptomatic treatment 7,8. In clinical practice, SIT is mostly performed by 50–80 subcutaneous injections (SCIT) of gradually increasing allergen doses over 3–5 years, leading to poor compliance rates 9. Also, the acceptance of SCIT is limited by local or systemic allergic side effects 10. "
[Show abstract][Hide abstract] ABSTRACT: Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection.
BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5-specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed.
Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells.
Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy.
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