The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis
ABSTRACT Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis.
We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway.
Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique.
Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04].
Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used.
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ABSTRACT: The prevalence of allergic diseases, such as rhinoconjunctivitis, is increasing worldwide, particularly in Westernized countries, where more than 30% of the population is affected. Insect venom allergy is also very common, affecting up to 5% of the population. Allergen-specific immunotherapy is the only immunomodulatory treatment that may alter the natural course of allergic disease, for example by preventing the development of asthma in rhinitic patients. Nonetheless, the risk-benefit ratio for subcutaneous immunotherapy has changed little from when it was first developed a century ago. However, the rapid evolution of new developments, including new methods of administration and new forms of antigen to stimulate the immune system, now offers improvements in both the safety and the efficacy of specific immunotherapy. These developments include the sublingual administration of the relevant antigens, which has a superior safety profile than the original subcutaneous route. This may enable higher dosages to be used over shorter treatment periods, with a lower risk of anaphylactic reactions. Improvements in the purity, specificity, and immunogenicity of the antigens, often as a result of advances in biotechnology, coupled with the development of new adjuvants, may further increase the efficacy of this form of treatment. This review describes and discusses these new developments in the context of the many recent advances in our understanding of the mechanisms by which immunotherapy appears to act.International Reviews Of Immunology 08/2009; 24(5-6):519-31. DOI:10.1080/08830180500370944 · 4.10 Impact Factor
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