Metabolomic Alterations Associated with Allergic Response in Equine Insect Bite Hypersensitivity

Background: Insect bite hypersensitivity (IBH) in horses involves an inappropriate immune response against mosquito-derived antigens, however, the exact cellular pathophysiological mechanisms are unclear.

Hypothesis/

Objectives: The cells affected by the immune response might leave specific biochemical fingerprints behind in the circulation, as they engage with this immune response. This study aimed to explore the serum metabolomic profiles of horses acutely suffering from an IBH reaction.

Animals: Thirty Icelandic horses classified as either healthy non-IBH controls or IBH cases.

Methods: Blood serum was collected in the summer from the healthy controls (n=15) and once in the summer (acute reaction, n=15) and once in the winter (latent phase, n=15) from the IBH cases. Samples were analyzed by untargeted chemical isotope labelling liquid chromatography-mass spectrometry and the obtained metabolomic profiles were subjected to partial least squares-discriminant analysis, t-tests, and pathway enrichment analysis.

Results: The metabolomic profiles clustered according to the clinical classification, i.e. healthy, acute, and latent. A total of 47 and 104 metabolites had a different abundance between the healthy and the acutely affected, and the acutely affected and latent IBH horses, respectively (FDR-adjusted P < .05). The former included 10 amino acids and derivatives, 8 peptides, and 10 fatty acids and derivatives, which were linked to 9 significantly altered metabolic pathways (P < .05).

Conclusions and clinical importance: IBH was associated with changes in the serum metabolomic profile. The metabolic pathway alterations can help explain the pathogenesis of IBH. The affected serum metabolites should undergo further validation for biomarker identification.