Chronic Inflammatory Bowel Disease (CIBD) and Celiac disease, are these linked in the horse?
Stehen chronisch entzündliche Darmerkrankungen (CIBD) und Zöliakie beim Pferd miteinander in Verbindung?
van den Hoven R, Thaller D, Bankuti P
Chronic inflammatory bowel disease (CIBD) is a disorder of the mucosa and submucosa characterized by infiltration of inflammatory cells. Diagnosis of the various forms is based on the degree of inflammation and the predominant type of infiltrating leucocytes. The cause of this abnormal cellular infiltrate has been linked to abnormal immune responses to bacterial, viral, parasitic, or dietary antigens. Celiac disease (CD) is a chronic inflammatory disease induced in genetically susceptible people by the ingestion of the irritant gluten and possibly modulated by other environmental cofactors. An abnormal immune response against gluten is the trigger for development of CD. CD is characterized by a large heterogeneity of clinical signs ranging from asymptomatic to severely symptomatic. Chemokine receptors play a fundamental role in leukocyte migration and one of the important chemokine receptors is CXCR3, which is expressed abundantly on human T-cells, and particularly on those T-cells associated with activation and inflammation. CXCR3 seems to play a role in equine immune response as well (Johnstone et al. 2016). Gliadins, the major gluten protein types, release zonulin after coupling to CXCR3. This subsequently results in increased permeability of the small intestinal mucosa and concurrent inflammation. A potential role of gluten in equine chronic inflammatory bowel disease was recently reported. The current pilot study aimed to show the expression levels of the CXCR3 receptor in small intestinal samples of healthy horses and horses histologically diagnosed with any of the disorders belonging to the CIBD syndrome. The electronic patient files of the University Equine Hospital of the Vetmeduni Vienna were searched for cases with protein‐losing enteropathy, weight loss, chronic enteritis and performed oral glucose tolerance tests. Furthermore, only cases from which intestinal samples had been kept in the repository were selected. Freshly collected small intestinal samples from 8 randomly chosen slaughter horses without any overt clinical signs were collected and used as control. Small bowel tissue was routinely stained with hematoxylin and eosin (HE) and the presence of CXCR3 in cells was shown by an in-situ immunofluorescence technique. Stained sections were analyzed using an Imager microscope and immunofluorescence of each individual slide was expressed as mean fluorescence intensity (MFI /µm2) using specific software. A total of 160 files with clinical histories of intestinal malabsorption, chronic weight loss or small intestinal inflammation were selected and further analyzed. Finally, only 7 cases fulfilled all criteria of equine CIBD. One of the cases had a concurrent adenocarcinoma of the caecum. One case showed histological signs of proliferative enteritis suggestive for infection with Lawsonia intracellularis, but the organism could no longer be detected in the sections. MFI was not significantly different between the diseased and the control group (p=0.613). One control horse reacted unexpectedly strong and was considered as unhealthy. Therefore, it was excluded from the control group. This pilot study showed that small intestinal mucosae of horses with histological lesions suggestive for CIBD did not express significantly more CXCR3 on cells in the gut walls than did randomly chosen slaughter horses. Therefore, this study could not prove that upregulation of CXCR3 on mucosal cells, possibly lymphocytes, is a specific response to gluten. Gluten allergy in the horse may be mediated by other cytokine receptors as well. Whether gluten allergy is the major cause of CIBD in horses cannot yet be concluded .