Neutrophil Extracellular Traps in Plasma from Dogs with Immune‐mediated Hemolytic Anemia

Lawson, Corinne; Smith, Stephanie A.; O'Brien, Mauria; McMichael, Maureen

doi:10.1111/jvim.14881

Cited by 24 publications

(29 citation statements)

References 55 publications

(92 reference statements)

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“…Samples were run in triplicate, and mean values used for statistical analysis, as previously reported (18, 68). Concentrations of plasma nucleosomes were analyzed using a commercial ELISA (Cell Death Detection ELISA Plus, Roche, Indianapolis, IN) scaled against pooled normal canine plasma because the assay lacks a reference standard (18, 68, 69). Plasma pooled from multiple normal dogs was analyzed in four wells on each plate and a reference value (assigned an arbitrary unit value of 1.0) was established as the mean of these four replicates.…”

Section: Methodsmentioning

confidence: 99%

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Martiny

Goggs

2019

Front. Vet. Sci.

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Septic peritonitis (SP) is common in dogs and is associated with high mortality. Early recognition is essential to maximizing survival and may be aided by biomarker measurement. The present study aimed to evaluate the ability of biomarkers to discriminate septic peritonitis from non-septic ascites (NSA). Eighteen dogs with SP and 19 age-matched controls with NSA were enrolled. Contemporaneous blood and peritoneal effusion samples were obtained. Concentrations of cell-free DNA (cfDNA), cytokines, glucose, lactate, N-terminal pro-C-type natriuretic peptide (NT-proCNP), nucleosomes, and procalcitonin (PCT) were measured using commercial reagents and assays. Paired biomarker concentrations were compared with the Wilcoxon matched-pairs signed rank test, and biomarker concentrations between groups were compared with the Mann-Whitney U -test. P -values were adjusted for multiple comparisons using the Bonferroni correction. Receiver operating characteristic curves were generated to assess the ability of the above biomarkers to discriminate SP from NSA. Dogs with SP had significantly greater blood CCL2 concentrations than dogs with NSA ( P = 0.032). Dogs with SP had significantly greater effusion CCL2, IL-6, IL-10, and lactate concentrations than dogs with NSA ( P ≤ 0.0121). Blood-effusion concentration gradients of CCL2, glucose, IL-6, IL-10, and lactate were significantly different in dogs with SP compared to dogs with NSA ( P ≤ 0.0165). Effusion lactate concentration had the highest AUROC value (0.866, 95% CI 0.751–0.980, P = 0.0001), although other biomarkers performed similarly. An effusion lactate concentration of 4.2 mmol/L was 72.2% (95% CI 46.5–90.3%) sensitive and 84.2% (95% CI 60.4–96.6%) specific for the diagnosis of SP.

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Section: Methodsmentioning

confidence: 99%

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Martiny

Goggs

2019

Front. Vet. Sci.

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“…Cattle were infected with OO L3 and venous blood samples were collected at days 0, 15 and 29 post infection. Serum was carefully harvested, without pigment contamination 96 . Serum sample (10 µL) was added to 90 µL of PBS, followed by addition of 100 uL of Sytox Green (1:200) per well in a black 96-well flat bottom plate (Nunc) and incubated in the dark for 15 minutes at RT.…”

Section: Methodsmentioning

confidence: 99%

Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi

Mendez

Sun

Tuo

et al. 2018

Sci Rep

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Ostertagia ostertagi (OO) is a widespread parasite that causes chronic infection in cattle and leads to annual losses of billions of dollars in the cattle industry. It remains unclear why cattle are unable to mount an effective immune response despite a large influx of immune cells to the infected abomasal mucosa and draining lymph nodes. Neutrophils, the immune system’s first responders, have the capacity to release neutrophil extracellular traps (NETs) to contain various pathogens, including some parasites. In the present study, the mechanisms by which O. ostertagi influences bovine NET formation were investigated. O. ostertagi larval soluble extract (OO extract) was able to induce typical NETs by purified neutrophils in vitro, confirmed by co-localization of extracellular DNA with typical NET-associated proteins histone and neutrophil elastase (NE). Consistent with existing literature, inhibition assays demonstrated that these OO extract-induced NETs were dependent upon the enzymes NADPH oxidase and myeloperoxidase (MPO). Live OO stage 4 larvae (L4) stimulated neutrophils to form NETs similar to those induced by OO extract. Bovine neutrophils also released NETs in response to Caenorhabditis elegans, a free-living soil nematode, suggesting that bovine NET production may be a conserved mechanism against a broad range of nematodes. This is the first report demonstrating O. ostertagi-induced NET formation by bovine neutrophils, a potentially underappreciated mechanism in the early immune response against nematode infections.

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“…A hypercoagulable state associated with IMHA is supported by a number of studies seeking to determine the underlying mechanism of altered hemostasis in this disease. A series of prospective controlled investigations (LOE 2, Good) identify increased tissue factor expression, platelet activation, procoagulant microparticles, and neutrophil extracellular traps, in dogs with IMHA compared to controls. Conversely, antiphospholipid antibodies were not implicated as a potential cause for thrombosis in dogs (LOE 2, Good) .…”

Section: Peco Question: Immune‐mediated Hemolytic Anemiamentioning

confidence: 99%

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1—Defining populations at risk

deLaforcade

Bacek

Blais

et al. 2019

J Vet Emergen Crit Care

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Objectives:Thrombosis is a well-recognized phenomenon in dogs and cats with a significant impact on morbidity and mortality. Despite growing awareness of thrombosis and increased use of antithrombotic therapy, there is little information in the veterinary literature to guide the use of anticoagulant and antiplatelet medications. The goal of Domain 1 was to explore the association between disease and thrombosis in a number of conditions identified as potential risk factors in the current veterinary literature, to provide the basis for prescribing recommendations.Design: A population exposure comparison outcome format was used to represent patient, exposure, comparison, and outcome. Population Exposure Comparison Outcome questions were distributed to worksheet authors who performed comprehensive searches, summarized the evidence, and created guideline recommendations that were reviewed by domain chairs. Revised guidelines then underwent the Delphi survey process to reach consensus on the final guidelines.Diseases evaluated included immune-mediated hemolytic anemia, protein-losing nephropathy, pancreatitis, glucocorticoid therapy, hyperadrenocorticism, neoplasia, sepsis, cerebrovascular disease, and cardiac disease.Settings: Academic and referral veterinary medical centers.

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Neutrophil Extracellular Traps in Plasma from Dogs with Immune‐mediated Hemolytic Anemia

Cited by 24 publications

References 55 publications

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Biomarker Guided Diagnosis of Septic Peritonitis in Dogs

Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 1—Defining populations at risk

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