Genetic linkage between the MHC gene region and immunoglobulin E levels against specific mould allergens in the horse

Immunoglobulin E (IgE) is an antibody class that mediates immediate type hypersensitivity reactions, which play an important role in the pathogenesis of some allergic diseases as well as in the defence against endoparasites. In the horse, IgE is probably involved in the pathogenesis of recurrent airway obstruction (RAO), a hypersensitivity reaction against moulds present in bay and straw. RAO-affected horses have significantly more often detectable serum IgE levels against the recombinant Aspergillus fumigatus allergens 7 and 8 (rAsp f 7 and rAsp f 8) than healthy horses. Although the environment, i.e. the exposure to allergens influences IgE levels, it is well known in man that the ability to produce high or low IgE responses is influenced by genetic factors. The heritability of 0.3 for mould-specific IgE has just been described in the horse. In man markers linked with atopy and/or high total serum IgE levels have been identified. The association between the equine MHC gene region and specific IgE levels against rAsp f 7 and rAsp f 8 has been investigated in 447 Lipizzan horses from six state studs (Austria, Croatia, Hungary, Italy, Slovakia and Slovenia) through typing of ELA A (MHC class I) locus and three microsatellite markers (HTG05, UM011 and HMS42) located on the same chromosome (ECA 20). Statistical analysis, based on composite models including four loci simultaneously, showed significant association of the ELA A and UM011 loci with IgE titres against rAsp f 7 and of UM011 with IgE titres against rAsp f 8. Furthermore, 76 Lipizzans from the Hungarian state stud were screened for two MHC class II loci (DQA and DRA) by SSCP. For IgE levels against rAsp, f 7 the composite model, including all six loci simultaneously, showed that the strongest association was found for DQA (P<0.01), while for rAsp f 8 specific IgE levels the strongest association was found with UM011 locus (P=0.01). UM011 is closely linked with the MHC class II locus DRB. In a population genetic study, highly significant correlation coefficients were obtained between alleles from ELA A, DQA, DRA and UM011. These results suggest that the MHC gene region influences the specific IgE response in the horse and are concordant with evidence obtained in human studies indicating that MHC class II genes control the specific IgE response against well-defined allergenic molecules. Our study does not allow distinguishing whether the specific IgE response is influenced by MHC class I or class II genes or by other closely linked genes in the horse, although the strongest associations were found with DQA and microsatellite UM011, which is closely linked with DRB. (Texte intégral)