Texas A&M Study on Protein-losing Enteropathy in Dogs

c7192013As part of DugDug’s ongoing series on leading researchers in veterinary research, we interviewed Dr. Niels Grützner, Dr.med.vet., a PhD student at the Gastrointestinal laboratory at Texas A&M University and Dr. Romy M. Heilmann, Dr.med.vet., a Veterinary Resident Instructor of Internal Medicine at the Small Animal Teaching Hospital at Texas A&M University. Their recent paper, titled Serum concentrations of canine alpha1-proteinase inhibitor in cobalamin-deficient Yorkshire Terrier dogs. was published in the journal Journal of Veterinary Diagnostic Investigation. The paper studies protein-losing enteropathy in dogs.

Please tell us about your background and research interests

NG: I am a veterinarian from Germany. After studying veterinary medicine at the College of Veterinary Medicine in Leipzig, Germany, I graduated with a veterinary degree (med.vet.) and obtained the license to practice veterinary medicine in 2005. After working a year in a private swine specialty practice, I returned to academia in spring of 2006 to work on a postgraduate doctoral degree in veterinary medicine (Dr.med.vet.). I have performed the research work for this degree at the Gastrointestinal Laboratory at Texas A&M University between 2006 and 2008, and I received the Dr.med.vet. degree soon after from the Ludwig-Maximilians-University in Munich, Germany. In fall of 2008, I enrolled into the PhD program at the Gastrointestinal Laboratory at Texas A&M University to enlarge and intensify my knowledge in the field of veterinary gastroenterology, and will finish the program by the end of 2013.

Due to my knowledge in the field of small and large animal medicine and particular in veterinary gastroenterology with reference to cobalamin (vitamin B12) metabolism, pancreatic function and gastrointestinal mucosal immunity my future goal is to work as a clinical researcher in the field of gastroenterology in small and large animal medicine.

What led you to this study?

NG: There were multiple factors involved: On one side it was the interest in the field of clinical veterinary gastroenterology (which I share with my wife Dr. Romy Heilmann), and on the other side because of our very own Yorkshire Terrier “Moses” who was and still is the driving force for the research we have done and will do in the future. Moses is a 7-year old male Yorkshire Terrier who has with episodes of vomiting and diarrhea, which we believe is due to a mild form of protein-losing enteropathy.

Protein-losing enteropathy which is a chronic gastrointestinal disease that is associated with excessive loss of proteins into the gastrointestinal tract as well as malabsorption of proteins and other nutrients such as cobalamin (vitamin B12). Protein-losing enteropathy has been reported to occur frequently in Yorkshire Terriers, and clinical signs observed in Yorkshire Terriers with PLE include diarrhea, vomiting, weight loss, and ascites. The exact pathogenesis of protein-losing enteropathy in the Yorkshire Terrier is unknown, and further research to better characterize and manage this disease is warranted and currently ongoing.

What were your findings?

In human medicine, the ratio between serum and fecal alpha1-proteinase inhibitor (commonly, abbreviated as: α1-PI), a biomarker that is quite stable in serum and in feces, is used as a diagnostic marker for protein-losing enteropathy. In comparison, in veterinary medicine we currently use the concentration of fecal α1-PI whereas the respective concentration in serum has not been considered in dogs with chronic gastrointestinal diseases. Therefore, in our study, we compared the serum alpha1-proteinase inhibitor concentration between two groups of Yorkshire Terriers. One group of Yorkshire Terriers that had a lack of cobalamin (vitamin B12) indicating a chronic gastrointestinal disease process and a second group of Yorkshire Terriers had normal serum cobalamin concentrations. The findings were that Yorkshire Terriers with a lack of cobalamin (suspected to be due to chronic gastrointestinal disease) had lower alpha1-proteinase inhibitor concentrations in serum than Yorkshire Terriers with normal serum cobalamin concentration. Using a different statistical approach we were able to show that decreased serum alpha1-proteinease inhibitor concentrations are associated with cobalamin deficiency in Yorkshire Terriers. The findings suggest that the serum biomarker alpha1-proteinase inhibitor in addition to the fecal value (and possibly also the ratio between these two) could be an important additional parameter for the characterization of chronic gastrointestinal disease in Yorkshire Terriers.

How can we use these findings?

Our initial investigation was conducted by using only serum samples from Yorkshire Terriers but the findings gave us a sense that it would be worth to look into the ratio between serum and fecal alpha1-proteinase inhibitor concentrations as described in humans. To date, no study has been conducted that evaluates serum and fecal alpha1-proteinase inhibitor concentrations as well as the ratio between these two in dogs with chronic gastrointestinal diseases such as protein-losing enteropathy. Again, protein-losing enteropathy has been reported to occur frequently in Yorkshire Terriers, which would be a great dog model to investigate this biomarker. Also, the Yorkshire Terrier is a well-known breed that has been ranked 5th position (on average) by the American Kennel Club over the last decade.

What do you plan to do with these findings?

Since for our study we had only serum samples available our next step is to collect serum and fecal samples from Yorkshire Terriers (and dogs of other breeds) with chronic gastrointestinal diseases such as protein-losing enteropathy at various veterinary clinics in North America (this collaborative multicenter study is currently ongoing). However, it is also important to collect serum and fecal samples from healthy dogs (Yorkshire Terriers) as well as from dogs with other gastrointestinal diseases to determine the clinical usefulness of this biomarker. Our hypothesis is that this biomarker will help to distinguish dogs with protein-losing enteropathy from healthy controls dogs and that it will be a prognostic factor.

What are ways to increase awareness around this?

As mentioned before, the Yorkshire Terrier is a well-known and high ranked dog breed in North America (and also in Europe), so there is a great interest from Yorkshire Terrier Kennel Clubs to further investigate and better characterize common diseases in the Yorkshire Terrier breed. Together with other veterinary clinics in North America and the Comparative Gastroenterology Society (CGS) we are working on various studies involving gastrointestinal diseases in companion animals such as protein-losing enteropathy (PLE) in Yorkshire Terriers. We have presented the results of our research at national and international meetings (such as the Annual Forum of the American College of Veterinary Internal Medicine and the Annual Meeting of the Comparative Gastroenterology Society [CGS]).

Any advice for people getting into your field?

Through our research in the field of companion animal gastroenterology, our work performed at the GI Lab at Texas A&M University, and through collaborations with other centers in North America, Europe, and other parts of the world we have learned that there is still much to be done in the field of veterinary gastroenterology. The interested reader is referred to the website of the CGS (http://vetmed.tamu.edu/cgs) and the GI Lab (http://vetmed.tamu.edu/gilab) where more information can be found about current research in the field of companion gastroenterology.

Please tell us a little more about your department

We are currently working at the Gastrointestinal Laboratory (GI Lab) at the Department of Small Animal Clinical Sciences/College of Veterinary Medicine and Biomedical Sciences at Texas A&M University. The GI Lab is a worldwide unique institution with emphasis on research in veterinary gastroenterology. We have developed several diagnostic tests that are used by veterinarians world-wide and we provide specialized testing services to help veterinarians diagnose and treat gastrointestinal diseases in dogs and cats. We are also one of the largest research groups in veterinary gastroenterology world-wide.