Gluten-dependent antibodies in horses with inflammatory small bowel disease (ISBD)

Abstract

Background: Equine inflammatory small bowel disease (ISBD) is an idiopathic pathologic condition seeming to increase in prevalence. Objective: To investigate the potential role of gluten in equine ISBD. Animals & Methods: Antibodies known to be important in the diagnosis of human coeliac disease (CD): IgA antibodies to human recombinant and guinea pig tissue-transglutaminase (TGA), native gliadin (AGA), deamidated-gliadin-peptides (DGPA), and primate and equine endomysium (EMA) were assessed in blood samples from three different groups of horses: ISBD affected (n ¼ 12) on a gluten-rich diet and controls either on gluten-rich (n ¼ 22) or gluten-poor (n ¼ 25) diets. Significant differences ( p < 0.05) between groups were assessed using the Wilcoxon test. Results: Both ISBD-affected horses and gluten-rich controls had significantly ( p < 0.0004) higher hrTGA titers than gluten-poor controls. However, ISBD horses did not show significantly increased levels of any of the CD related antibodies when compared to gluten-rich controls. Nevertheless, markedly increased antibody levels (TGA, EMA and DGPA) were found in one of the ISBD horses. The introduction of a gluten-free ration in this 14-year-old warmblood stallion resulted after 6 months in the reduction of antibody levels and clinical recovery associated with improved duodenal histopathology. Conclusion: To the best of our knowledge, this is the first study assessing gluten-related antibodies in horses and results suggest a potential pathogenic role of gluten in at least some cases of equine ISBD. Clinical importance and impact for human medicine: Given serology and concurrent clinical findings, this study warrants further investigations into the immunologic basis of possible gluten-sensitive enteropathy in horses and analogy with human disease.

Can the outcome of an impaired oral glucose absorption test in horses be improved with fat supplementation and dietary modifications?

“…Consequently, colic, laminitis and endotoxaemia are commonly seen in cases of increased fermentation of non-structural carbohydrates in equines 25 55–57. Among the many pathologies related to gastrointestinal inflammation in horses, preliminary findings suggest that an immunological reaction similar to gluten sensitivity enteropathy could also occur 7. However, further research is necessary to better understand this pathological condition.…”

“…The aetiology of IBD is unknown, but the nature of the inflammatory infiltrate has been linked to an abnormal immune-mediated response against certain factors such as parasites, ingested antigens, tumour cells or even wheat 7. Infectious agents (such as Mycobacterium avium , M paratuberculosis and Lawsonia intracellularis ) producing inflammation and malabsorption syndrome have also been reported 4 8–10.…”

The role of animal models in unravelling therapeutic targets in coeliac disease

“…Both species develop hallmarks of CD such as partial villus atrophy, increased IEL and anti-TG2 antibodies (only in macaques). A recent study also described the occurrence of spontaneous inflammatory small bowel disease in horses with partial villus atrophy that was ameliorated after six months of GFD [18]. Following gluten sensitization, other animal species, namely mice and rats, are used to study gluten-dependent enteropathies.…”

Using Animal Models of Celiac Disease to Understand the Role of MHC II

“…Therefore, it is still possible that specifi c MHC II alleles may be associated with the gluten-dependent enteropathy in the monkey model, but with time this possibility becomes less likely. The recent publication that characterized a single horse association with MHC is uncertain [ 18 ]. Of the three spontaneous animal models, then, MHC II molecules may be necessary for the development of gluten-dependent enteropathy, but specifi c alleles that exclusively contribute to the development of infl ammatory gluten-responsive T cells do not appear to be present as is found in CD (humans).…”