Antihistone Autoantibodies in Dobermans With Hepatitis

Dyggve, H.; Meri, Seppo; Spillmann, Thomas; Jarva, Hanna; Speeti, M.

doi:10.1111/jvim.14838

Cited by 10 publications

(31 citation statements)

References 41 publications

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“…Recent studies have shown evidence that the development of chronic hepatitis in Dobermanns has an autoimmune component . High hepatic copper concentrations cause or contribute to progression of chronic hepatitis.…”

Section: Discussionmentioning

confidence: 99%

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs

Mandigers

Watson³

et al. 2019

Veterinary Internal Medicne

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Background Hepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations. Objectives To investigate whether the ATP7A :c.980C>T and ATP7B :c.4358G>A mutations identified in Labrador Retrievers were associated with hepatic copper concentrations in Dobermanns. Animals Dobermanns from the Netherlands (n = 122) and the United States (n = 78). Methods In this retrospective study, mutations in ATP7A and ATP7B were investigated as risk factors for hepatic copper accumulation in Dobermanns. Liver biopsies of 200 Dobermanns were evaluated by histochemical copper staining, quantitative copper measurement, or both modalities. ATP7A and ATP7B genotypes were obtained by Kompetitive Allele Specific PCR. A linear regression model was used to investigate an association between genotype and hepatic copper concentrations. Results The ATP7A :c.980C> T was identified in both Dutch (2 heterozygous individuals) and American Dobermanns. In the American cohort, the minor allele frequency of the mutation was low (.081) and a possible effect on hepatic copper concentrations could not be established from this data set. A significant association of the ATP7B :c.4358G>A variant with increased hepatic copper concentrations in Dobermanns was observed. Conclusions and Clinical Importance The ATP7B :c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper‐associated hepatitis in breeds other than the Labrador Retriever.

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Section: Discussionmentioning

confidence: 99%

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs

Mandigers

Watson³

et al. 2019

Veterinary Internal Medicne

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“…Specific criteria for the diagnosis of immune‐mediated hepatitis in dogs have not been developed. An immune basis in some dogs with idiopathic CH is suggested by several criteria (Table ) which include the presence of lymphocytic infiltrates in the liver, abnormal expression of major histocompatibility complex class II proteins, positive serum autoantibodies, familial history of liver disease, association with other immune‐mediated disorders, female predisposition, and favorable response to immunosuppression . A presumptive clinical diagnosis of immune‐mediated CH in the dog requires elimination of other etiologies and a favorable response to immunosuppressive treatment.…”

Section: Etiologymentioning

confidence: 99%

“…Details and evidence for breed, sex, and age predispositions are summarized in Supporting Information Table S1. There is strong evidence in ≥2 studies for an increased prevalence of CH in BT, Doberman Pinschers, LR, Dalmatians, American and English Cocker Spaniels, English Springer Spaniels, and West Highland White Terriers in several countries. In addition, in Sweden the Scottish Terrier, and in the United Kingdom the Cairn Terrier, Great Dane, Samoyed, Yorkshire Terrier, and Jack Russell Terrier are predisposed .…”

Section: Signalment and Clinical Signsmentioning

confidence: 99%

“…An immune basis in some dogs with idiopathic CH is suggested by several criteria (Table 5) which include the presence of lymphocytic infiltrates in the liver, abnormal expression of major histocompatibility complex class II proteins, positive serum autoantibodies, familial history of liver disease, association with other immune-mediated disorders, female predisposition, and favorable response to immunosuppression. 1,7,9,14,15,20,32,34,[146][147][148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163]165,167,168 A presumptive clinical diagnosis of immune-mediated CH in the dog requires elimination of other etiologies and a favorable response to immunosuppressive treatment. Currently, the lack of commercially available tests to detect liver-specific antibody-antigen interactions or cell immunosensitization in dogs with CH limits the definitive determination of an immune-mediated etiology.…”

Section: Immune-mediated Chmentioning

confidence: 99%

See 1 more Smart Citation

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

Webster

Cullen

Penninck

et al. 2019

Veterinary Internal Medicne

198

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This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.

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“…31 More recently, autoantibodies against liver proteins were found in sera of Doberman pinschers with CH before the onset of clinical signs. 32 Using an indirect immunofluorescence assay on cryostat sections of mouse liver small numbers of Doberman's with CH had evidence of antinuclear antibodies, 33 and IgG autoantibodies against histones. 34 However, the question that remains from all these studies is whether these autoantibodies are the primary cause of the disease, or a secondary phenomenon.…”

Section: Etiologymentioning

confidence: 99%

Canine Idiopathic Chronic Hepatitis

Bexfield

2017

Veterinary Clinics of North America: Small Animal Practice

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The author has nothing to disclose. Synopsis/AbstractKey Points  Canine idiopathic hepatitis is a common disease, categorized histologically by presence of hepatocellular apoptosis or necrosis, a variable mononuclear or mixed inflammatory cell infiltrate, regeneration and fibrosis. Key WordsIdiopathic; hepatitis; canine; diagnosis; management; prognosis  Clinical signs are vague and non-specific, but there are known breed, age and gender predispositions. Results of clinical pathology are non-specific, but usually include elevations in liver enzymes and function impairment; a liver biopsy is required for diagnosis. Management involves around the use of an anti-inflammatory dose of glucocorticoids and other supportive and symptomatic therapies including ursodeoxycholic acid, antioxidants, diuretics, and diet. The prognosis is variable, but there are known prognostic indicators, especially the presence of portal hypertension.

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Antihistone Autoantibodies in Dobermans With Hepatitis

Cited by 10 publications

References 41 publications

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

Canine Idiopathic Chronic Hepatitis

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