Serum Thymidine Kinase 1, Canine‐C‐Reactive Protein, Haptoglobin, and Vitamin D Concentrations in Dogs with Immune‐Mediated Hemolytic Anemia, Thrombocytopenia, and Polyarthropathy

Grobman, Megan; Outi, Hilton; Rindt, Hansjörg; Reinero, Carol R.

doi:10.1111/jvim.14787

Cited by 22 publications

(37 citation statements)

References 30 publications

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“…This study corroborates previous findings that dogs with certain IMD had significantly decreased 25(OH)D concentrations (38). To the authors' knowledge, this is the first study to compare Vitamin D levels with survival in dogs with IMD.…”

Section: Discussionsupporting

confidence: 92%

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

2019

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Background: Low vitamin D increases the risk of immune-mediated disease (IMD) in human beings and rodent models. Vitamin D metabolites, particularly 1,25(OH)2D3, modulate gene expression of immune cells and may attenuate immune pathways that drive IMD. Hypothesis/objectives: Our primary hypothesis was that serum 25(OH)D3 and 1,25(OH)2D3, are reduced in patients with IMD and associate with poorer outcomes. We secondarily hypothesized serum 24,25(OH)2D3 would not be associated with disease or outcome. We also measured serum CXCL10 concentrations to determine if an increase occurs in dogs with IMD and in association with poorer survival. Animals: We enrolled dogs diagnosed with IMD ( n = 29) and healthy control dogs ( n = 9) in the study with informed client consent. Methods: Serum was collected and stored at −80°C until analyses. Serum vitamin D metabolites were measured by LC-MS/MS by an accredited laboratory. A commercially available canine-specific ELISA kit measured serum CXCL10. Results: Serum 25(OH)D3 and 1,25(OH)2D3 were significantly reduced in dogs ( n = 25) with IMD. Serum CXCL10 concentrations undetectable in all controls, and were 30 times higher overall in IMD dogs ( n = 25; P = 0.004). CXL10 was, however, undetectable in 40% of dogs with IMD. Of the 60% of IMD dogs with increased CXCL10 concentrations, 5/25 had concentrations at the upper limit of quantification. The survival of those five dogs was significantly ( P = 0.049) shorter (72 days) than all other dogs with IMD with measured CXCL10 concentrations. The median survival time (MST) for dogs with 25(OH)D3 concentrations ≤ the median was 106 days, while dogs with concentrations of 25(OH)D3 > the median did not achieve an MST. Conclusions and clinical importance: Serum 25(OH)D3 and 1,25(OH)2D3, but not 24,25(OH)2D3 levels are reduced dogs with IMD. Vitamin D metabolites and CXCL10 may be useful prognostic markers and may be targets for adjunct therapy in canine IMD. These data support the future investigation of vitamin D analogs in the treatment of canine IMD.

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Section: Discussionsupporting

confidence: 92%

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

2019

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“…Dogs have similar co-morbidities (e.g., endocrinopathies, hyperlipidemia, cholecystitis), and surgical interventions for biliary disease. Likewise, vitamin D in dogs, like humans, has potent immunologic effects and can predict outcome in various diseases highlighting an overlap in vitamin D physiology [38][39][40][41][42]. There are several differences in vitamin D metabolism that would strengthen the use of dogs as a model.…”

Section: Introductionmentioning

confidence: 99%

Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele

et al. 2020

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Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Gallbladder hypokinesia has been proposed to contribute to its formation and progression. The specific cause of gallbladder stasis in dogs with GBM as well as viable treatment options to resolve dysmotility remains unknown. Vitamin D deficiency is one of the many potential causes of gallbladder hypokinesia in humans and repletion results in complete resolution of stasis. Improving our understanding of the relationship between serum vitamin D and GBM could help identify dogs as a model for humans with gallbladder hypokinesia. Furthermore, this relationship could provide insight into the pathogenesis of GBM and support the need for future studies to investigate vitamin D as a novel treatment target. Therefore, goals of this study were i) to determine if serum 25-hydroxyvitamin(OH)D concentrations were decreased in dogs with GBM, ii) if serum 25(OH)D concentrations were different in clinical versus dogs subclinical for GBM, and iii) to determine if serum 25(OH)D concentrations could predict the ultrasonographic type of GBM. Sixty-two dogs (clinical, n = 26; subclinical, n = 36) with GBM and 20 healthy control dogs were included in this prospective observational study. Serum 25(OH)D concentrations were measured with a competitive chemiluminescence immunoassay. Overall, dogs with GBM had lower serum 25(OH)D concentrations than control dogs (P = 0.004). Subsequent subgroup analysis indicated that this difference was only significant in the subclinical group compared to the control dogs (P = 0.008), and serum 25(OH)D concentrations did not significantly differ between dogs clinical for GBM versus subclinical or control dogs, indicating that inflammatory state in clinical dogs was not the major constituent of the observed findings. Decreasing serum 25(OH)D concentrations, but not clinical status, was associated with a more advanced developmental stage of GBM type determined by ultrasonography. Our results indicate that vitamin D has a role in dogs with GBM. Additional studies are needed to assess if reduced vitamin D in dogs with GBM is a cause or effect of their biliary disease and to investigate if vitamin D supplementation could be beneficial for dogs with GBM.

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“…In veterinary medicine, there has been interest in leveraging protein biomarkers such as thymidine kinase type 1 (TK1), canine C-reactive protein (cCRP), and alpha-fetoprotein receptor (RECAF) for canine cancer detection ( 153 , 154 ); however, such protein biomarkers are not highly specific for canine cancer and can be elevated due to other reasons including immune-mediated hemolytic anemia, thrombocytopenia, and polyarthropathy ( 155 ). In human medicine, protein biomarkers such as RECAF and AFP have demonstrated limited sensitivity and specificity for cancer detection ( 143 , 156 ).…”

Section: Liquid Biopsy: the Next Frontier In Veterinary Cancer Carementioning

confidence: 99%

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

Chibuk¹,

Flory²,

Kruglyak³

et al. 2021

Front. Vet. Sci.

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Cancer is the leading cause of death in dogs, in part because many cases are identified at an advanced stage when clinical signs have developed, and prognosis is poor. Increased understanding of cancer as a disease of the genome has led to the introduction of liquid biopsy testing, allowing for detection of genomic alterations in cell-free DNA fragments in blood to facilitate earlier detection, characterization, and management of cancer through non-invasive means. Recent discoveries in the areas of genomics and oncology have provided a deeper understanding of the molecular origins and evolution of cancer, and of the “one health” similarities between humans and dogs that underlie the field of comparative oncology. These discoveries, combined with technological advances in DNA profiling, are shifting the paradigm for cancer diagnosis toward earlier detection with the goal of improving outcomes. Liquid biopsy testing has already revolutionized the way cancer is managed in human medicine – and it is poised to make a similar impact in veterinary medicine. Multiple clinical use cases for liquid biopsy are emerging, including screening, aid in diagnosis, targeted treatment selection, treatment response monitoring, minimal residual disease detection, and recurrence monitoring. This review article highlights key scientific advances in genomics and their relevance for veterinary oncology, with the goal of providing a foundational introduction to this important topic for veterinarians. As these technologies migrate from human medicine into veterinary medicine, improved awareness and understanding will facilitate their rapid adoption, for the benefit of veterinary patients.

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Serum Thymidine Kinase 1, Canine‐C‐Reactive Protein, Haptoglobin, and Vitamin D Concentrations in Dogs with Immune‐Mediated Hemolytic Anemia, Thrombocytopenia, and Polyarthropathy

Cited by 22 publications

References 30 publications

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

Serum 25-hydroxyvitamin D concentrations in dogs with gallbladder mucocele

Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs

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