GI Biomarkers Flashcards
Classification of biomarkers
functional, biochemical,
cellular,
genomic,
proteomic,
metabolomic,
microbiomic,
behavioural, or outcome biomarkers
𝞪1 protease inhibitor - what is it and what are pros/cons
Major proteinase inhibitor that is primarily synthesised in the liver. Molecular mass is similar to albumin but is not hydrolysed by intestinal bact.
Lost in faeces in dogs with PLE at similar rate to albumin
Pros - Useful for early detection of protein loss as increases before clinical signs or in dogs with low albumin but no other GI signs
80% PPV for PLE in dogs with CIE (3 day avg) and 90% NPV
Cons - large day to day variation so need to pool sample.
Specificity not great as can see increase in other disease or if giving steroids
Citrulline - what is it and what are pros/cons
Citrulline is a non dietary amino acid involved in intermediary metabolism produced almost exclusively by the enterocytes of the small intestinal mucosa. For this reason,plasma or serum citrulline concentrations have been proposed as a biomarker of small bowel mass and function
Pros - decrease in parvovirus consistent with functional change to gut
Cons - Serum citrulline was of no prognostic value in parvovirus infected dogs.
Failed to distinguish healthy dogs and dogs with CE or to stratify the different subtypes of CE including dogs with PLE in a recent study
Utility of CRP in intestinal disease
nonspecific marker of inflammation
High biological variability of serum CRP concentrations in dogs limits its utility as a diagnostic biomarker in dogs with CIE. Appears to be clinically more useful as a surrogate marker of clinical severity to assess disease progression and response to treatment
Recent study found that a serum CRP concentration ≥ 9.1 mg/L distinguished dogs with CIE requiring anti-inflammatory or immuno- suppressive treatment from those dogs responding to an elimination diet or antibiotic trial with a sensitivity of 72% and a specificity of 100%.
Decreased after treatment of CIE
- Correlated with AHDS severity score
- Higher in dogs with gastric neoplasia compared to those with gastritis
pANCA- what is it and what are pros/cons
Serum autoantibodies against neutrophil granule components and suspected cross-reactivity with a gastrointestinal bacterial antigen
Pros - Seropositivity for pANCA (and also pANCA titers) is higher in dogs with FRE (61%-62%) than in those with IRE or NRE
associated with PLE/PLN in SCWT 95% sens 80% specificity
Cons - can be increased with other immune mediated disease
Does not improve with Tx of CIE
3-Bromotyrosine - what is it and pros/cons
A stable metabolite of eosinophil peroxidase, which is released from eosinophils after their activation and degranulation
Pros - may differentate CIE dogs needing immunosuppression from those that are food responsive
Cons - increased by other disease states
Sens/Spec not determined
Calprotectin -what is it and pros/cons
DAMP that accumulates at sites of inflammation.
Expressed and released by activated macrophages and neutrophils,but expression also can be induced in epithelial cells
Pros - can be measured in faeces, surrogate marker of disease severity. PPV (77%) and NPV (82%) for faecal calprotectin to identify PR/NR from complete response
Cons - Serum levels are not specific for intestinal disease. Faecal levels increase with acute adn chronic GI disease
Also affected by corticosteroid use
Calgranulin C -what is it and pros/cons
Also a DAMP - but has number of targets and central role in innate response
Pros - not affected by corticosteroids (unlike calprotectin)
NPV >80% for predicting NR from complete response
Also elevated in cats with CE and GI lymphoma
Cons - increased by other GI disease
Causes of hyperlipidaemia
- Primary: Min Schnauzer, Rottweiler, Doberman, LPL deficiency in cats
- Secondary: drugs (steroids, phenobarbital); endocrine (DM, HAC, hypoTH); pancreatitis; PLN; cholestasis; hepatic insufficiency
Postprandial
Sequelae of hyperlipidaemia
Pancreatitis
Hepatobiliary disease - vacuolar hepatopathy, lipidosis, GBM
Insulin resistance - resolves with Tx in Min Schnauz
Ocular cahnges
Neurological dysfunction
Renal proteinuria
Subclinical low grade inflammation - independently associated with increased serum calprotectin (DAMP)
Fenofibrate - use and MOA
Increases lipoprotein lipase concentrations and activity –> clearance of LDL
Treatment of hyperlipidaemia refractory to dietary management in dogs and cats.
Mild GI upset reported in 1 or 2 animals depending on study. Remainder had no adverse effects
May increase risk of cholelithiasis due to increased biliary clearance of cholesterol
What is Secretory testing, and how is it interpreted
measurement of fasting gastric pH and concurrent measurement of serum gastrin levels
pH <3 and elevated gastrin levels can occur with gastrinoma, and rules out the possibility of achlorhydria or MCT
