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    Neuer Therapieansatz zur Behandlung des Sommerekzems beim Pferd auf molekularbiologischer und immunologischer Ebene (2014)

    Art
    Hochschulschrift
    Autor
    Kühnel, Silvia (WE 5)
    Quelle
    Berlin: Mensch und Buch Verlag, 2014 — 127 Seiten
    ISBN: 978-3-86387-528-2
    Verweise
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000097545
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    +49 30 838 51833
    viro@zedat.fu-berlin.de

    Abstract / Zusammenfassung

    Summer eczema in horses represents a seasonal recurrent allergic dermatitis to the insect’s salivary proteins of Culicoides biting midges. Clinical symptoms of affected horses include itching, alopecia and skin lesions, resulting in a diminished usability of up to 50% during the flight time of the insect from March to October. In addition, horses with summer eczema suffer from a lot of strain. Therapeutical treatment can be very individualans all therapies are approach only and every horse can react distinctly. State of the art therapy can only reduce clinical symptoms, yet a cure of summer eczema is still to be found.
    This work is thought to found a new therapeutical approach for the treatment of summer eczema in horse. On the basis of a therapeutical called TACI-Ig used to remedy human autoimmune diseases a strategy was developed to transfer the effective mechanism to the equine model. TACI-Ig neutralizes its pro-inflammatory cytokine ligands BAFF and APRIL, resulting in impaired maturation, functioning and survival of B cells, increases the apoptosis rate of these cells and thereby inhibiting their development into B cells as well as the consecutive production of immunoglobulins. As a result, no inflammatory molecules will be released from mast cells. A systemic administration of equine TACI-Ig (eTACI-Ig) could inhibit mechanisms relevant for development and sustentation of this disease.
    In this study eTACI-Ig was developed via PCR amplificationthe of the extracellular part of TACI from horse DNA and coupling it to the FC region of an equine immunoglobulin. The resulting fusion protein eTACI-Ig was tested for functionality by means of neutralizing its ligands equine BAFF and APRIL, which were also produced in the context of this work. ELISA tests clearly showed binding of eTACI-Ig to eBAFF and eAPRIL, proving the functionality of the newly synthesized fusion protein in vitro.
    Goal of this project was to transfer knowledge of the immune system of horses and the disease mechanisms to an effective approach for therapeutical treatment and potential cure of summer eczema by eTACI-Ig. Further ex and in vivo functionality tests are needed, e.g. the ex vivo study of its impact on various cell types and equine immunoglobulins on the base of fresh horse blood. Additionally, in vivo efficacy, dose responses and tolerance need to be determined. Although, production of big amounts of TACI-Ig can be difficult and expensive, its necessary in order to finally treat summer eczema systemically in horses.
    A successful treatment of summer eczema with eTACI-Ig could potentially give rise to treatment and curation of other allergic illnesses in horses and would be a fundamental break-through in horse medical science.