Evaluation of perinuclear anti-neutrophilic cytoplasmic autoantibodies as an early marker of protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers

Allenspach, Karin; Lomas, Bethany; Wieland, Barbara; Harris, Tyler; Pressler, Barrak M.; Mancho, Carolina; Lees, George E.; Vaden, Shelly L.

doi:10.2460/javma.233.7.1089

Cited by 7 publications

(18 citation statements)

References 7 publications

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“…However, pANCA seropositivity is not specific for CIE and also can occur with other immune-mediated, infectious, or neoplastic diseases 101,102. Positivity for pANCA is associated with PLE, protein-losing nephropathy, or both in Soft Coated Wheaten Terriers, with pANCA positivity being detected >2 years before the onset of hypoalbuminemia 103. Although pANCA is a difficult assay to acquire, it might be useful for diagnosing dogs with FRE and for early detection of protein-losing disease in Soft Coated Wheaten Terriers (where fecal α 1 PI also might predict gastrointestinal protein loss before the development of hypoalbuminemia).…”

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confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

108

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Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food‐responsive, antibiotic‐responsive, or immunosuppressant‐responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein‐losing enteropathy. Disease‐independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1‐proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C‐reactive protein, perinuclear anti‐neutrophilic cytoplasmic antibodies, 3‐bromotyrosine, N‐methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

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confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

108

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“…Details regarding these 38 patients can be found in a previously reported study. 5 Agreement between the two methods was assessed by testing a subset of 10 samples by the same person (KA), using both assays.…”

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confidence: 99%

“…10 Studies involving a cohort of softcoated wheaten terriers (SCWT) and SCWT-beagle crossbred dogs with PLN/PLE indicated that antibodies appeared up to 2 years before development of clinically relevant disease, suggesting possible use of ANCA to predict onset of disease. 5 Titers for ANCA remained positive once identified. These various studies suggest that ANCA testing could be utilized for a number of immune-mediated disease syndromes although an assay designed for dogs is not currently widely available.…”

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confidence: 97%

“…2,3 After increasing use in the human medical field, ANCA have been documented in diseases of dogs associated with an inappropriate immune response, including canine inflammatory bowel disease, protein-losing enteropathy/nephropathy (PLE/PLN), immunemediated hemolytic anemia, and vasculitis-related illness. [4][5][6][7] Antineutrophil cytoplasmic antibodies have been documented in patients with neoplastic and infectious diseases. 6,8 Chronic enteropathies are well documented ANA antinuclear antibodies cANCA cytoplasmic antineutrophil cytoplasmic antibodies FRD food-responsive disease IIF indirect immunofluorescence MPO myeloperoxidase protein pANCA perinuclear antineutrophil cytoplasmic antibodies PLE protein-losing enteropathy PLN protein-losing nephropathy PR-3 proteinase-3 protein SCWT soft-coated wheaten terrier SRD steroid-responsive disease in veterinary medicine and have been divided into diseases that are responsive to dietary management alone (termed "food-responsive disease," [FRD]), antibiotic therapy (termed "antibiotic-responsive disease"), or diseases that require immunosuppressive drugs for control of clinical signs (termed "steroid-responsive disease,"…”

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confidence: 99%

“…After increasing use in the human medical field, ANCA have been documented in diseases of dogs associated with an inappropriate immune response, including canine inflammatory bowel disease, protein‐losing enteropathy/nephropathy (PLE/PLN), immune‐mediated hemolytic anemia, and vasculitis‐related illness . Antineutrophil cytoplasmic antibodies have been documented in patients with neoplastic and infectious diseases .…”

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Use of a Granulocyte Immunofluorescence Assay Designed for Humans for Detection of Antineutrophil Cytoplasmic Antibodies in Dogs with Chronic Enteropathies

Florey

Viall

Streu

et al. 2017

Veterinary Internal Medicne

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BackgroundPerinuclear antineutrophil cytoplasmic antibodies (pANCA) previously have been shown to be serum markers in dogs with chronic enteropathies, with dogs that have food‐responsive disease (FRD) having higher frequencies of seropositivity than dogs with steroid‐responsive disease (SRD). The indirect immunofluorescence (IIF) assay used in previous publications is time‐consuming to perform, with low interobserver agreement.Hypothesis/ObjectivesWe hypothesized that a commercially available granulocyte IIF assay designed for humans could be used to detect perinuclear antineutrophil cytoplasmic antibodies in dogs.AnimalsForty‐four dogs with FRD, 20 dogs with SRD, 20 control dogs, and 38 soft‐coated wheaten terrier (SCWT) or SCWT‐cross dogs.MethodsA granulocyte assay designed for humans was used to detect pANCA, cANCA, and antinuclear antibodies (ANA), as well as antibodies against proteinase‐3 protein (PR‐3) and myeloperoxidase protein (MPO) in archived serum samples.ResultsSensitivity of the granulocyte assay to predict FRD in dogs was 0.61 (95% confidence interval (CI), 0.45, 0.75), and specificity was 1.00 (95% CI, 0.91, 1.00). A significant association was identified between positive pANCA or cANCA result and diagnosis of FRD (P < 0.0001). Agreement between the two assays to detect ANCA in the same serum samples from SCWT with protein‐losing enteropathy/protein‐losing nephropathy (PLE/PLN) was substantial (kappa, 0.77; 95% CI, 0.53, 1.00). Eight ANCA‐positive cases were positive for MPO or PR‐3 antibodies.Conclusions and Clinical ImportanceThe granulocyte immunofluorescence assay used in our pilot study was easy and quick to perform. Agreement with the previously published method was good.

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Preliminary evaluation of serum zonulin in canine chronic enteropathies

Dinesh

Slovak

Kogan

et al. 2022

J of Small Animal Practice

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In humans, serum zonulin, a biomarker of intestinal permeability, correlates with underlying enteropathies and has potential application as a therapeutic target. The aim of this study was to evaluate serum zonulin as a biomarker for canine chronic enteropathy.Materials and MethOds: Prospective enrolment of twenty-one client-owned dogs with at least 1 of the following gastrointestinal (GI) signs for at least 3 weeks duration: anorexia, hyporexia, dysrexia, vomiting, weight loss or diarrhea. 21 control dogs, age and breed matched, were also enrolled. Dogs with gastrointestinal signs were diagnosed with chronic enteropathy based on a complete blood count, serum chemistry, specific canine pancreatic lipase, cobalamin, resting cortisol, abdominal ultrasound and gastrointestinal endoscopy with histopathology. Enrolled control dogs had an unremarkable physical examination, complete blood count, serum chemistry and no clinical signs of gastrointestinal disease. Dogs were ineligible if antibiotics or immunosuppressive medications were administered within 1 month of enrolment. Blood samples were analysed using a commercial canine serum zonulin quantitative ELISA.results: Dogs with chronic enteropathies had median serum zonulin values of 0.28 ng/mL (interquartile range: 0.04-2.59), while control dogs of 0.27 ng/mL (0.05-3.67). There was no significant difference in canine serum zonulin levels between these populations. The estimated difference in the median concentrations was −0.01 ng/mL (95% CI: −0.23 to 0.89).clinical significance: In this study, using a commercial canine zonulin ELISA, serum zonulin levels did not differentiate between dogs with chronic enteropathies and control dogs.

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Evaluation of perinuclear anti-neutrophilic cytoplasmic autoantibodies as an early marker of protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers

Abstract: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Cited by 7 publications

References 7 publications

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Use of a Granulocyte Immunofluorescence Assay Designed for Humans for Detection of Antineutrophil Cytoplasmic Antibodies in Dogs with Chronic Enteropathies

Preliminary evaluation of serum zonulin in canine chronic enteropathies

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