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Pathogenetic and immunological aspects of equine allergic diseases in relationship to their genetic basis

English title Pathogenetic and immunological aspects of equine allergic diseases in relationship to their genetic basis
Applicant Marti Schalch Eliane
Number 116803
Funding scheme Project funding (Div. I-III)
Research institution Abteilung für Klinische Forschung Dept. für klinische Veterinärmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Veterinary Medicine
Start/End 01.04.2007 - 31.03.2010
Approved amount 227'000.00
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All Disciplines (2)

Discipline
Veterinary Medicine
Genetics

Keywords (6)

allergy; horse; insect bite hypersensitivity; regulatory cells; recombinant allergens; genetics

Lay Summary (English)

Lead
Lay summary
The immunological mechanisms leading to the increased incidence of allergic diseases in western industrialised countries have not been elucidated yet. Allergic diseases involve the interaction of 3 major factors: 1. genetic constitution, 2. exposure to allergens, and 3. immunoregulatory mechanisms determined by 1. and 2, but also influenced by other factors. We have a unique natural model to study these factors: Insect bite hypersensitivity (IBH) is an allergic dermatosis of the horse caused by bites of insects (Culicoides spp). There are at least ten different allergens in the saliva of these insects but they have not been characterised at the molecular level yet. IBH does not occur in Iceland, due to the lack of Culicoides spp. but the prevalence of IBH is >50% in Icelandic horses born in Iceland and imported into continental Europe as adults. Conversely, the prevalence of IBH in Icelandic horses born in Europe, where Culicoides spp. are present, is 5-10%. A genetic predisposition for IBH has been documented in various breeds. However, in Icelandic horses, additional factors play a crucial role in susceptibility or resistance to IBH, such as being born in an environment where the causative allergens are present or absent. We hypothesise that other factors specific to the Icelandic environment such as a higher endoparasite burden in horses living in Iceland and the absence of some equine viral diseases may also contribute to the high prevalence of IBH in horses born in Iceland and exported to Europe. We have observed that lymphocytes of IBH-affected horses express significantly higher levels of T helper 2 (Th2)-cytokines than those of healthy horses, and that horses born in Iceland and imported to Switzerland express significantly higher levels of Th2-cytokines than Icelandic horses matched with regard to disease state but born in Switzerland. We hypothesize that this relative suppression of Th2 cytokines in horses born in Switzerland is due to regulatory T cells (Treg). Our aim is to characterize Treg and their cytokines in the horse and test whether they determine disease incidence in Icelandic horses. We will also investigate which environmental factors can contribute to the high prevalence of IBH in horses exported from Iceland. We shall also clone and express the specific Culicoides allergens as recombinant proteins. Significance the project. IBH is a natural disease allowing the study of the natural course of allergy in an outbred but genetically well defined population. Besides providing new insights into the pathogenesis of allergic diseases, in the future this project will allow the study of how the immune response before or after exposure to allergens (Culicoides) can be influenced by preventive immunization or immunotherapy and thus improve treatment of IBH.Experimental design / methods: 1.characterize Treg in the horse and test whether Treg determine disease incidence in Icelandic horses. 2.Follow a group of horses imported from Iceland to Switzerland and measure immunological parameters before exposure to Culicoides until outbreak of disease. 3.Collect samples for genetic studies.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
129837 Pathogenic and immunological aspects of equine allergic diseases in relationship to their genetic basis 01.05.2010 Project funding (Div. I-III)
138295 Immunology and genetics of equine recurrent airway obstruction and defence against nematodes 01.10.2011 Project funding (Div. I-III)

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