T helper 1 (Th1), Th2 and regulatory T (Treg) cells as well IgE-mediated signaling pathways factors 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. 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), sIgG(4), 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. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) 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. 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.
COBISS.SI-ID: 29977049
Our project group validated microRNA quantitative measurement by including let-7b, miR-126, miR-9, and miR-19a probes in complex lung cancer model. With this validation we were able to exactly follow the dynamic of miR-15b, miR-21 in miR-150 in miR-155 in paired samples of our long-term follow-up project. Those microRNAs might be included in regulation of SAP/SLAM gens, which are involved in differentiation of T-cells with immunoregulatory properties, notably invariant NKT cells, which promote Th1 biased CD4 T lymphocyte response and may have a very important role in type 1 diabetes and in sarcoidosis.
COBISS.SI-ID: 30144729
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. 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). 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. 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.
COBISS.SI-ID: 30233305