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

Pathogenesis of Rhinitis

Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called ‘idiopathic’ (previously ‘vasomotor’) rhinitis. Allergic rhinitis affects approximately 1 in 4 of the population of westernised countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptive immunity together with environmental factors is likely to play major roles. In allergic rhinitis, initial allergen exposure and sensitization involves antigen presenting cells, T and B lymphocytes and results in the generation of allergen-specific T cells and allergen specific IgE antibodies. On re-exposure to relevant allergens crosslinking of IgE on mast cells results in the release of mediators of hypersensitivity such as histamine and immediate nasal symptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 T lymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phase allergic response. Evidence for nasal priming and whether or not remodelling may be a feature of allergic rhinitis will be reviewed. The occurrence of so-called ‘local’ allergic rhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE mediated) rhinitis will be considered in the context of inflammatory and non-inflammatory disorders

A modern approach to establishment of photogrammetric control points problem

The ground control points for aerial photogrammetry - how it was done 40 years ago, 20 years ago and how it is done today with the help of GPS instrumentation. Modern methods show their advantage both in time consuming and accuracy. The use o f GPS allows to solve large scale mapping problems that appear in towns, railways, highways etc

Researching the accuracy of hand held GPS receivers

Analizując wyniki wyznaczania współrzędnych x, y, pojedynczego punktu ręcznym odbiornikiem GPS, można stwierdzić występowanie składnika systematycznego. Okoliczność ta występuje dla różnych typów odbiorników, w różnych miejscach kraju, dla różnych układów odniesienia. Usunięcie składnika systematycznego ze zbioru obserwacji pozwala uzyskać zmniejszenie błędów prawdziwych wyznaczenia położenia punktu. Na dokładność wyznaczenia położenia współrzędnych punktu mają też wpływ różne inne czynniki: liczba widocznych nad horyzontem satelitów, jakość geometrii wyznaczenia (PDOP), wykorzystanie systemu EGNOS, czynniki zakłócające oraz czas pozyskiwania wyników na stanowisku. Analizując tę ostatnią przyczynę, ustalono na podstawie badań, że wiarygodne wyniki otrzymuje się dopiero po około 2 minutach od rozpoczęcia obserwacji na stanowisku.Analysing the results of determining x, y coordinates of a single point position by GPS hand held receiver leads to find out a systematic component. It exists for different types of receivers, in different provinces, in different reference systems. Elimination of this bias from the set of observations makes it possible to diminish true values of errors of determination of point location. There are some other different sources of errors in determination of point location: number of satellites in view, quality of their geometry (PDOP), using EGNOS system, multipath errors and also observation time at the station. Researching the latter error it was found out, that reliable results are optainable after 2 minutes since the observation started

The effect of prolonged measuring time on accuracy of point position fixed with RTK GPS technique in ASG-EUPOS system

Rozważane są skutki wydłużenia czasu obserwacji w przypadku wyznaczania współrzędnych pojedynczego punktu techniką RTK GPS przy współpracy z systemem ASG-EUPOS. Wnioski oparte są na analizie wyników 2 prac badawczych, jakie niezależnie prowadzono celem ustalenia takiej zależności.The paper deals with effects of prolonged measuring time of observation in case of fixing single point position with RTK GPS in co-operatin with active geodetic network ASG-EUPOS. The conclusions are based on 2 independent research works done specially to solve this problem. Both investigations show clear dependence between the time of measurement and the accuracy of positioning in case of single reference ASG-EUPOS station at the distance less than 5 km. For distances longer than 10 km; when the impact of distance dependent errors prevails, it is not recommended to extend measuring time over 10 seconds. Further investigations should be done to show more precisely to what extend (between 5 and 10 km) is it worth to extend the time of measurement

Surface Impedance Boundary Conditions applied to solving nonlinear electrodynamic systems

The paper presents a method for solving electromagnetic field problems by applying impedance boundary conditions for systems including conducting bodies of nonlinear magnetic properties in an excited harmonic field. Three types of impedance boundary conditions were derived. A procedure for computing surface impedance based on the transfer matrix is proposed. This procedure has been tested by comparing computational results to calculations where time function distortions were considered, and to the experimental data