ABSTRACT
BACKGROUND: The precise immunological mechanisms for the early clinical protection of venom immunotherapy (VIT) have not yet been explained. Our aim was to evaluate whether high-affinity IgE receptor (FcεRI) and the related basophil function have a role in the induction of short-term VIT protection. METHODS: We included 60 adults and 48 children. Basophil threshold sensitivity (CD-sens) to anti-FcεRI stimulation, and FcεRI gene and cell-surface expression were assessed at the beginning and just before the first maintenance dose (MD) of 100 µg of ultra-rush VIT (day 5) and at the beginning, during buildup, and just before the first MD of 70 µg and of 100 µg of semi-rush VIT (weeks 1-2 and 5). RESULTS: We demonstrated a significant reduction in CD-sens to anti-FcεRI stimulation before the first MD in both ultra-rush and semi-rush VIT in all included subjects. FcεRI gene and/or cell-surface expression was decreased in 34-100% of subjects, with different dynamics between VIT protocols. CONCLUSION: We found a marked desensitization of FcεRI-activated basophils after short-term VIT. This suppression, which could be highly relevant for the development of early protective mechanisms, might be also related to the changes at the level of FcεRI expression.
Subject(s)
Basophils/immunology , Basophils/metabolism , Desensitization, Immunologic , Receptors, IgE/metabolism , Venoms/immunology , Adolescent , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Basophils/drug effects , Child , Child, Preschool , Female , Gene Expression Profiling , Humans , Hypersensitivity/genetics , Hypersensitivity/immunology , Hypersensitivity/therapy , Insect Bites and Stings , Leukocyte Count , Male , Middle Aged , Receptors, IgE/genetics , Receptors, IgE/immunology , Venoms/administration & dosage , Young AdultABSTRACT
BACKGROUND: Interleukin (IL)-15 is an important mediator in chronic inflammatory diseases. Recently, we have described the association of IL-15 haplotypes with bronchial asthma. Asthma genetics is highly complex - about every second candidate gene is not confirmed in consecutive studies. We were interested in whether association of asthma with IL-15 holds in a second population. Furthermore, we sought to investigate the effect of different controls. METHODS: Five IL-15 polymorphisms were genotyped on the German Multicenter Allergy Study (MAS) cohort consisting of 886 children who were followed up from birth to 10 years of age. At 10 years of age, 96 were found to be asthmatic. MAS children who never had any wheezing symptoms (n = 576), who were never diagnosed with asthma (n = 790) and 129 super controls who had never had any atopic disorder were used as controls. Finally, 270 randomly chosen adults served as controls. RESULTS: Association was confirmed with single polymorphism and haplotypes. The super controls showed the highest difference to the asthmatics regarding haplotype frequencies. However, the effect escaped statistical significance, most likely because of the small sample size. CONCLUSION: Association of IL-15 with asthma was confirmed. Although super controls might be the most suitable, more numbers are needed. This might hamper the value of these controls especially when investigating common diseases.
