Gastrointestinal Immunology

Background: The detailed pathological phenotype of diet-responsive chronic enteropathy (CE) and its modulation with dietary therapy remain poorly characterized.Hypothesis/Objectives: Key mucosal lesions of diet-responsive CE resolve with dietary therapy.Methods: This was a prospective observational study of 20 dogs with diet-responsive CE. Endoscopic duodenal biopsies collected before and 6 weeks after the start of a dietary trial were assessed by means of qualitative and quantitative histopathological, immunohistochemical, and ultrastructural criteria. Control duodenal biopsies were obtained from 10 healthy Beagle dogs on 1 occasion.Results: Compared with control dogs, the CE dogs had higher villus stunting scores and higher overall WSAVA scores, a lower villus height-to-width ratio, and higher lamina propria density of eosinophils. The CE dogs also had ultrastructural lesions of the mitochondria and brush border. In common with other studies in which the disease and control populations are not matched for breed, age, sex, and environment, these comparisons should be interpreted with caution. Comparing biopsies collected at presentation and 6 weeks after starting the dietary trial, mean lamina propria mononuclear cell score and lamina propria densities of eosinophils and mononuclear cells decreased. Dietary therapy also improved ultrastructural lesions of the mitochondria and brush border, eliciting a decrease in intermicrovillar space and an increase in microvillus height.Conclusions and Clinical Importance: In dogs with diet-responsive CE, the remission of clinical signs with dietary therapy is associated with subtle decreases in lamina propria density of eosinophils and mononuclear cells, and resolution of ultrastructural lesions of the enterocyte.

Section: Discussionmentioning

confidence: 93%

A Comprehensive Pathological Survey of Duodenal Biopsies from Dogs with Diet‐Responsive Chronic Enteropathy

Walker

Knuchel-Takano

McCutchan

et al. 2013

“…The largest immunologic organ is the GI tract, where immunologic barrier function plays a vital role in maintaining homeostasis. The gut‐associated lymphoid tissue (GALT) consists of the intestinal lamina propria cells, intraepithelial lymphocytes, Peyer's patches, and mesenteric LNs . Lymphocytes continuously recirculate from the bloodstream into intestinal lymph through GALT, to exert immune control in almost all tissues .…”

Section: Lymphatic Structure and Functionmentioning

confidence: 99%

Comparative pathophysiology and management of protein‐losing enteropathy

Craven

Washabau

2019

116

Protein‐losing enteropathy, or PLE, is not a disease but a syndrome that develops in numerous disease states of differing etiologies and often involving the lymphatic system, such as lymphangiectasia and lymphangitis in dogs. The pathophysiology of lymphatic disease is incompletely understood, and the disease is challenging to manage. Understanding of PLE mechanisms requires knowledge of lymphatic system structure and function, which are reviewed here. The mechanisms of enteric protein loss in PLE are identical in dogs and people, irrespective of the underlying cause. In people, PLE is usually associated with primary intestinal lymphangiectasia, suspected to arise from genetic susceptibility, or “idiopathic” lymphatic vascular obstruction. In dogs, PLE is most often a feature of inflammatory bowel disease (IBD), and less frequently intestinal lymphangiectasia, although it is not proven which process is the true driving defect. In cats, PLE is relatively rare. Review of the veterinary literature (1977‐2018) reveals that PLE was life‐ending in 54.2% of dogs compared to published disease‐associated deaths in IBD of <20%, implying that PLE is not merely a continuum of IBD spectrum pathophysiology. In people, diet is the cornerstone of management, whereas dogs are often treated with immunosuppression for causes of PLE including lymphangiectasia, lymphangitis, and crypt disease. Currently, however, there is no scientific, extrapolated, or evidence‐based support for an autoimmune or immune‐mediated mechanism. Moreover, people with PLE have disease‐associated loss of immune function, including lymphopenia, severe CD4+ T‐cell depletion, and negative vaccinal titers. Comparison of PLE in people and dogs is undertaken here, and theories in treatment of PLE are presented.

“…The effector sites of GALT, the epithelium and lamina propria, carry out elimination, tolerance, and inflammatory responses before antigen interaction at the inductive sites. 47 IEL and LPL are primarily T lymphocytes and show significant phenotypic and functional differences. 48 The similarity between the peripheral and duodenal lamina propria immunophenotypes and the uniqueness of the intestinal epithelial T subpopulations in dogs have been described previously.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peripheral and intestinal T lymphocyte subsets in dogs with chronic inflammatory enteropathy

Agulla,

Villaescusa,

Sainz

et al. 2024

BackgroundDysregulated T lymphocyte response is thought to play a key role in chronic intestinal inflammation (CIE).ObjectivesTo evaluate the presence of changes in peripheral and intestinal T lymphocyte subsets and to describe potential immune and inflammatory biomarkers in dogs with CIE.AnimalsSixteen healthy dogs and 26 dogs were diagnosed with CIE.MethodsProspective case‐control study evaluating peripheral and intestinal T lymphocytes using flow cytometry and inflammatory markers obtained from complete blood cell counts.ResultsDogs with CIE had higher peripheral activated T helper (Th) lymphocytes (87/μL [18‐273] CIE, 44/μL [16‐162] healthy control (HC, P = .013) and regulatory T cells (Treg; 108/μL [2‐257] CIE, 34/μL [1‐114] HC, P = .004). In the intestinal epithelium, CIE dogs presented lower percentages of Th (4.55% [1.75‐18.67] CIE, 8.77% [3.79‐25.03] HC, P = .002), activated Th cells (0.16% [0.02‐0.83] CIE, 0.33% [0.05‐0.57] HC, P = .03) and CD4/CD8 ratio (0.08 [0.02‐0.39] CIE, 0.21 [0.07‐0.85] HC, P = .003). Conversely, higher percentage of activated T cytotoxic cells (20.24% [3.12‐77.12] CIE, 12.32% [1.21‐39.22] HC, P = .04) and interferon‐gamma (IFN‐γ) producing T lymphocytes (7.36% [0.63‐55.83] CIE, 1.44% [0.00‐10.56] HC, P = .01) within the epithelium was observed. In the lamina propria the percentage of Treg lymphocytes was higher (6.02% [1.00‐21.48] CIE, 3.52% [0.18‐10.52] HC, P = .02).Conclusions and Clinical ImportanceSystemic and intestinal immune alterations occur in dogs with CIE suggesting that blood IFN‐γ producing T lymphocytes and the systemic immune‐inflamation index (SII) could potentially serve as biomarkers for the disease.