Omalizumab may decrease IgE synthesis by targeting membrane IgE+ human B cells

Omalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. In vitro studies and animal models support the hypothesis that omalizumab inhibits IgE synthesis by B cells and causes elimination of IgE-expressing cells either by induction of apoptosis or induction of anergy or tolerance. METHODS: We examined the influence of omalizumab on human tonsillar B cell survival and on the genes involved in IgE synthesis. Tonsillar B cells were stimulated with IL-4 plus anti-CD40 antibody to induce class switch recombination to IgE production in the presence or absence of omalizumab. Cell viability was assessed and RNA extracted to examine specific genes involved in IgE synthesis. CONCLUSIONS: We found that omalizumab reduced viable cell numbers but this was not through induction of apoptosis. IL-4R and germline Cϵ mRNA levels were decreased as well as the number of membrane IgE+ cells in B cells treated with omalizumab. These data suggest that omalizumab may decrease IgE synthesis by human B cells by specifically targeting membrane IgE-bearing B cells and inducing a state of anergy

FAST: Towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication

[Introduction to] : "Sustainability of constructions : integrated approach to life-time structural engineering"

The main objective of the COST Action C25 ‘Sustainability of Constructions: Integrated Approach lo Life-time Structural Engineering” is to promote science-based developments in sustainable construction in Europe through the collection and collaborative analysis of scientific results concerning life-time structural engineering and especially integration of environmental assessment methods and tolls of structural engineering.Sustainability of Construction, European Science Foundation : Cost C2

A robust 18-pulse diode rectifier with coupled reactors

The article presents the principle of operation and selected results of simulation and laboratory tests of the 18-pulse rectifier system with coupled reactors and small series active power filter. The presented system makes it possible to reduce, especially in distribution supply networks, undesired higher current harmonics. The 18-pulse nature of operation of the rectifier is reached using a set of coupled three-phase network reactors (CDT and CTR). The simultaneous use of the coupled reactors and the small active power filter provides opportunities for reduction of the supply current distortion, especially in case of voltage harmonic distortion and voltage unbalance