Summary of Research
Clinical Gastroenterology
Canine Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) in the dog is associated with chronic diarrhoea, weight loss and in severe cases with protein losing enteropathy (PLE). The consequences of chronic diarrhoea and associated ill-thrift are serious, both for the dog and for its owners, and treatments are largely palliative at present. Although there are significant differences between canine IBD and its human counterparts, Crohn’s disease and ulcerative colitis, in all these diseases the current paradigm is that inflammation occurs due to a loss of immune tolerance to normal intestinal microbial flora and food-derived antigens. Although changes in immune-cell populations, inflammatory cytokine mRNA expression and latterly epithelial tight junction protein expression have been reported in canine IBD, the events leading up to theses alterations remain poorly elucidated. Based on the premise that intestinal epithelial barrier dysfunction may be involved in the generation of an aberrant immune response in canine IBD, research into epithelial tight junction expression is ongoing, in conjunction with a project evaluating intestinal epithelial cell apoptosis. We are also about to embark on a pilot project evaluating faecal and urinary metabolomic profiling in dogs with chronic enteropathies.
Clinical Haematology
Characterisation of antibody responses to bone marrow precursor cells in dogs with non-regenerative anaemia
We are increasingly seeing dogs being referred for investigation of severe non-regenerative anaemia, for which there is an inadequate reticulocyte response. Based on exclusion of other disease processes that are known to result in non-regenerative anaemia (e.g. iron deficiency, chronic renal failure, bone marrow infiltration with neoplastic cells) and due to responsiveness to immunosuppressive therapies, some of these individuals have been diagnosed as having non-regenerative immune-mediated haemolytic anaemia. On evaluation of bone marrow from these patients we often observe an apparent maturation arrest at the level of the red cell precursors, and the assumption is that antibodies are targeted at the level of the erythrocyte precursors (Weiss 2008). Unfortunately, we also see a cohort of dogs with similar clinical and bone marrow characteristics that fail to respond to immunosuppressive therapy. We have no current explanation for the pathogenesis of anaemia in these cases although they may also represent and immune-mediated disease with poor response to therapy. This pilot project involves evaluation of bone marrow archive tissue for the presence of antibodies targeting erythrocyte precursors and will be conducted by a summer student in collaboration with Prof. Elspeth Milne.
T-regulatory cells in Canine Immune-mediated Haematological Disorders
Immune-mediated haemolytic anaemia (IMHA) and immune-mediated thrombocytopenia are relatively common haematological disorders in the dog. Although the clinical presentations are well-characterised the aetio-pathogenesis of these diseases are poorly defined, although strong breed associations suggest a genetic influence. Based on the observations that a number of human immune-mediated haematological disorders are associated with altered T-regulatory cell function, Prof. Elspeth Milne and I have funding for a pilot project evaluating lymphocyte subpopulations, in particular the CD4+CD25+Foxp3+ regulatory cells, in the peripheral blood of dogs with immune-mediated haematological disorders.
Other areas of Interest
Faecal Colonisation with ESBL-producing Escherichia coli in a hospitalised population of dogs
Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli) and other gram-negative enteric bacteria (Enterobacteriaceae) are emerging pathogens in human medicine, where they are associated with increased morbidity and mortality, particularly in high-dependency and intensive care units. Their emergence has largely been blamed on the overuse and misuse of antibiotics, although other factors are likely to contribute. We are currently conducting a study to determine the prevalence of colonisation with ESBL-producing bacteria in dogs admitted to, and discharged from the HFSA ICU. By reviewing clinical data including antibiotic therapy and by characterising resistance genes in faecal isolates we hope to establish risk factors for colonisation. This study has been funded by an Edinburgh Alumni Grant and is being conducted in collaboration with Dr Sally Argyle.