Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Insect bite hypersensitivity or “IBH” is an allergic reaction to salivary antigens from Culicoides species and possibly other insects. It is the most common allergic disease in horses and it seriously reduces the commercial value as well as the welfare of affected horses. Until now, no curative treatment is available but clear indications exist that the susceptibility for IBH is partly heritable. Therefore, the genetic basis of IBH susceptibility in Belgian Warmblood Horses (BWP) was investigated in this PhD study. A quantitative as well as a molecular genetic analysis were combined.At the start of this project, information about IBH prevalence and/or about risk factors affecting IBH prevalence in BWP horses was not available. Therefore, 3409 IBH records stabled in Belgium were collected by means of a questionnaire at sport competitions, BWP breeding days, breeder visits and telephone calls. Horses were classified as IBH affected or unaffected based on owner statement. The average IBH prevalence in BWP included in the present study was 10%. Since 70% of IBH affected horses were treated with preventive measure to reduce clinical symptoms and 38% of IBH affected horses did not show clinical symptoms at the time of questioning, the average prevalence of IBH symptoms was only 6.2%. The most important risk factors for IBH in BWP were age and the type of surrounding vegetation. The number of horses owned by a horse owner (=stud size) also largely affected the (reported) IBH prevalence. The knowlegde about which non-genetic factors affect IBH prevalence was used to infer genetic parameters of IBH susceptibility in BWP horses. Horses were classified as IBH affected based on two different criteria: 1) on a lifetime record based on owner information and 2) on whether or not the horse showed symptoms at the time of questioning. Heritabilities were estimated using both threshold (animal and sire) and a linear animal model. Heritabilities on the underlying scale obtained in threshold models were between 0.65 and 0.78, depending on which statistical model, dataset or criterion to classify IBH affected horses was used. The heritability on the observed scale was 0.53 when estimated with a linear animal model and between 0.18 and 0.26 when transformed from posterior means obtained in different threshold models. The dataset structure and the criterion to classify IBH affected horses influenced correlation coefficients between estimated breeding values obtained with different statistical models. Additionaly, a molecular genetic analysis was performed to identify mutations associated with IBH susceptibility. For this, the candidate gene approach was chosen in which DNA of IBH-affected horses (cases) was compared to DNA of IBH-unaffected horses (controls). The level of discrimination between the selected control and case group affects the chances to identify molecular markers associated with IBH. To avoid misclassification of horses and support the classification of IBH affected and unaffected horses, the performance of a diagnostic serological test was evaluated. Allergen-specific IgE levels against Culicoides nubeculosus thorax extract (‘NubTH’), Obsoletus group whole body extract (‘ObsWBE’), seven C. nubeculosus and two Obsoletus group recombinant proteins were measured in 343 warmblood horses. A combination of the IgE levels against the three best performing Culicoides spp. recombinant proteins and ObsWBE resulted in the best performing test (‘CulSumOf3_Obs’). The accuracy of the test increased when clinical signs at sampling were more pronounced or when the IBH history could be considered as classical. When IBH affected horses showing severe clinical signs at sampling and with a classical IBH history were compared to IBH unaffected horses, the Youden’s index at the optimal cut-off for CulSumOf3_Obs was 0.67. This optimal cut-off had a sensitivity of 70%, a specificity of 97% and a total accuracy of 92%. CulSumOf3_Obs could be used to support the selection of IBH affected and unaffected horses for a molecular genetic analysis.Three candidate genes were selected for genetic characterization based on their function and on the fact that homologous genes in humans are associated with allergic diseases with similar immunopathological characteristics as IBH. These genes code for the interleukin-4 receptor (IL-4R), the CC-chemokine RANTES and filaggrin (FLG). The expression levels of IL-4R and RANTES were determined in peripheral blood mononuclear cells (PBMC), but no differential expression was found (p=0.58 and p=0.63 respectively). When expression of RANTES and FLG was investigated in skin biopsies, no significant expression differences for FLG were found. However, a sequencing experiment revealed that the sequence provided by Ensembl for the FLG cDNA sequence was wrongly annotated. In addition, downregulation of RANTES was observed in skin biopsies of IBH-affected horses as compared to controls (p=0.0008) and mares had significantly higher RANTES mRNA level than stallions and geldings, independently from their IBH status (p=0.0008). In conclusion, IBH susceptibility is a heritable trait in BWP with a high heritability coefficient. Therefore, it should be possible to identify IBH susceptible horses using estimated breeding values. However, in order to obtain reliable estimated breeding values, IBH records should be collected routinely and this should preferably be organised using a questionnaire and face-to-face contact between investigator and horse owner. However, identification of IBH susceptible horses at a young age or under environmental circumstances in which IBH symptoms do not occur will only be possible when molecular markers associated with IBH susceptibility will be identified.

Cheval --- horses --- Piqûre d'insecte --- Insect stings --- Immunologie --- Immunology --- Réaction allergique --- Hypersensitivity --- diagnosis --- Academic collection --- 636.122 --- Thoroughbreds --- Theses --- 636.122 Thoroughbreds