Evaluation of Prognostic Factors, including Duodenal P-Glycoprotein Expression, in Canine Chronic Enteropathy

SIMPLE SUMMARY: Canine chronic enteropathies are classified according to their response to diet, antibiotics, and immunosuppressant drugs, or to a lack of response to treatment. The aim of this study was to identify which factors, including P-glycoprotein activity (a membrane-bound protein involved in multiple drug resistance), could be related to therapeutic failure. Ninety-two dogs were included in the study (73 with immunosuppressant-responsive enteropathy and 19 with non-responsive enteropathy). Factors significantly associated with an increased risk of belonging to the non-responsive group are previous treatment with glucocorticoids and hypoproteinemia. Moreover, using clonality testing, approximately one quarter of the non-responsive dogs showed a clonal response for T or B lymphocytes in the duodenal lymphocytes, although both histology and immunohistochemistry were not suggestive of lymphoma. In conclusion, additional studies are needed to investigate the underlying mechanisms that cause the non-responsive enteropathy, and whether a latent neoplastic disease could be related to the lack of response. ABSTRACT: The aim of this retrospective single-center study was to evaluate which factors, including expression of P-glycoprotein (P-gp), a membrane-bound protein involved in multiple drug resistance, could predict the response to treatment in canine immunosuppressant-responsive enteropathy (IRE). Dogs with IRE or non-responsive enteropathy (NRE) that were examined from 2005 to 2014 were included and were divided into two groups (IRE vs. NRE). Signalment, history, and clinical and laboratory findings were collected. P-glycoprotein immunohistochemistry was carried out on duodenal biopsies of both groups stored in our biobank, and immunophenotyping and molecular clonality were performed on the NRE samples. Ninety-two dogs were enrolled, 73 IRE (79.3%) and 19 NRE (20.7%), with a prevalence of pure breed (78.3% vs. 21.7%) and male dogs (p < 0.001). Factors associated with a worse prognosis were previous treatment with steroids (p = 0.033) and lower serum total protein concentration (p = 0.005). Clonality testing on the NRE duodenal biopsies showed 5/16 clonal responses, assuming a latent undiagnosed lymphoma as a possible cause of the NRE.