Search

Background: Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Methods: Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG4, nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Results: Decreased wheal sizes and VAS scores, negative challenges and increased sIgG4 levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Conclusions: Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Treatment failure of venom immunotherapy (VIT) is not rare and the risk and pathogenic factors for those failures are so far poorly understood. For that reason we evaluated allergen-specific basophil sensitivity in patients who did not tolerate field re-stings after completed VIT treatment. Methods: Basophil responsiveness was evaluated by flow cytometry analyses of basophil CD63 surface expression induced by different concentrations of bee or wasp venom (1, 0.1 and 0.01 μg/ml) in 14 treated patients who had experienced systemic allergic reactions (Muller grades II–III) and 17 treated patients who had no reactions after the field re-stings. We also included a group of 28 Hymenoptera venom-allergic patients who had not received VIT. Results: In 14 patients who still reacted to bee or wasp sting, basophil response at a venom concentration of 0.1 μg/ml was significantly higher than in patients who tolerated field re-stings (p = 0.03; t test). Basophil response was also slightly higher at a concentration of 1 μg/ml, but not to statistical significance (p = 0.12; t test). There was no difference in the response to direct cross-linking of the IgE and in venom-specific IgE and IgG4 serum concentrations between those 2 groups (p > 0.8; Fisher’s exact test, t test). Patients who tolerated field re-stings have also significantly lower basophil response in comparison to patients who had not received VIT, both at 0.1 and 1 μg/ml of venom concentrations (p < 0.001; t test). Conclusions: The results suggest that basophil venom-specific sensitivity is associated with the efficiency of VIT. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]