Evaluation of Serum 3‐Bromotyrosine Concentrations in Dogs with Steroid‐Responsive Diarrhea and Food‐Responsive Diarrhea

Sattasathuchana, Panpicha; Allenspach, Karin; Lopes, Rosana; Suchodolski, Jan S.; Steiner, Jörg M.

doi:10.1111/jvim.14742

Cited by 17 publications

(21 citation statements)

References 31 publications

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“…Dogs with CIE have increased serum 3‐BrY concentrations,106 with dogs requiring anti‐inflammatory or immunosuppressive treatment having higher serum 3‐BrY concentrations compared to dogs responding to an elimination diet 107. However, sensitivity and specificity of the serum 3‐BrY concentration to differentiate dogs with IRE or NRE from those with FRE or ARE have not been determined.…”

Section: Biomarkers In Chronic Inflammatory Enteropathies Of Dogsmentioning

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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Section: Biomarkers In Chronic Inflammatory Enteropathies Of Dogsmentioning

confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Veterinary Internal Medicne

108

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“…3,5 Recent advances in the diagnosis of CIE include the development of a 6-parameter 6 (considering the dog's attitude/activity, appetite, vomiting, feces consistency, feces frequency, and weight loss; the cumulative score can range from 0 to 18) and a 9-parameter clinical scoring system 7 (which considers the dog's attitude/activity, appetite, vomiting, feces consistency, feces frequency, weight loss, serum albumin concentration, ascites/peripheral edema, and pruritus; the cumulative score can range from 0 to 27), an endoscopic lesion score, 8 and a consensus for classifying CIE based on histopathologic criteria. 3,9 However, only a few minimally or noninvasive biomarkers of inflammation have been evaluated in dogs with CIE, [10][11][12][13][14][15][16][17][18] none of which are currently routinely used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

Heilmann

Berghoff

Mansell

et al. 2018

Veterinary Internal Medicne

107

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BackgroundCalprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown.ObjectiveEvaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE.Animals127 dogs.MethodsProspective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR).ResultsFecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%).Conclusions and Clinical ImportanceFecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.

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“…CE can be subclassified into 3 categories: food-responsive diarrhea, antibiotic-responsive diarrhea, and steroidresponsive diarrhea. 1,15 However, dogs with CE in our study were not classified into these 3 subtypes, which is a limitation of our study. Nonetheless, the development of a less invasive modality to diagnose CE may still prove to be beneficial for early diagnosis and treatment without the need to perform an intestinal biopsy.…”

Section: Discussionmentioning

confidence: 86%

“…16 Furthermore, other studies have reported elevated serum 3-BrY concentrations in dogs with CE. 15,17 Serum markers, unlike those in fecal samples, are not specific to the GI tract. Various other markers for GI diseases, such as canine alpha 1 -proteinase inhibitor, calprotectin, N-methylhistamine, and S100A12, are measured in fecal samples to assess patients with CE.…”

Section: Introductionmentioning

confidence: 99%

Analytical validation of fecal 3-bromotyrosine concentrations in healthy dogs and dogs with chronic enteropathy

et al. 2019

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Studies that have used serum 3-bromotyrosine (3-BrY) to investigate eosinophil activation in dogs have found elevated 3-BrY levels in clinical patients with chronic enteropathy (CE). To our knowledge, a method to measure 3-BrY concentrations in feces has not been reported. We developed and analytically validated an electron ionization gas chromatography-mass spectrometry method to measure fecal 3-BrY concentrations in dogs. The mean and maximum fecal 3-BrY concentrations in healthy dogs (n = 40) and dogs with CE (n = 40) over 3 consecutive days were compared. Analytical validation had a limit of blank and a limit of detection of 2.5 and 3.7 mmol/g of feces, respectively. The mean coefficients of variation for precision and reproducibility for 3-BrY were 11.2% (range: 7.5-14.2%) and 10.1% (4.8-15.2%), respectively. The ranges of observed-to-expected ratios for linearity and accuracy were 81.3-125% and 85.4-120%, respectively. The reference intervals for mean and maximum fecal 3-BrY concentrations in 40 healthy dogs were 3.7-23.0 and 3.7-37.8 mmol/g of feces. Mean and maximum fecal 3-BrY concentrations in dogs with CE were significantly higher than those of healthy dogs (p < 0.001). Further research is warranted to determine the clinical usefulness of fecal 3-BrY concentrations in dogs with CE.

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Evaluation of Serum 3‐Bromotyrosine Concentrations in Dogs with Steroid‐Responsive Diarrhea and Food‐Responsive Diarrhea

Cited by 17 publications

References 31 publications

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

Analytical validation of fecal 3-bromotyrosine concentrations in healthy dogs and dogs with chronic enteropathy

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