Evaluation of DLA promoters in Doberman hepatitis

Abstract

Doberman hepatitis (DH) is associated with homozygous DLA-DRB1*00601/DQA1*00401/DQB1*01303 indicating a role for the immune system in the development of the disease. The dog leucocyte antigen (DLA) class II expression is controlled at the transcriptional level with proximal promoters. Differential expression of DLA class II molecules of antigen-presenting cells is reported to affect susceptibility to or protection from different immune-mediated diseases. The aim of this study was to evaluate, whether the variation in promoter areas of homozygous DLA-DRB1*00601/DQA1*00401/DQB1*01303 Dobermans could explain why some dogs become afflicted with DH and others do not. Our findings suggest that promoter variants are not associated as risk modifiers in homozygous DLA-DRB1*00601/DQA1*00401/DQB1*01303 Dobermans, but additional factors are needed. Nevertheless, our study indicates that the whole DLA block is associated to the disease.

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

“…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.…”

“…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 .…”

“…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.…”

“…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, 24,35 Doberman Pinschers, 7,20,[43][44][45]150,[153][154][155][156]158,162,[169][170][171][172][173] LR, 8,10,14,21,27,138,158,162,163,168,169,172 Dalmatians, [39][40][41]157,158,169,174 American and English Cocker Spaniels, 27,48,156,157,162,163,165,169,175 English Springer Spaniels, 158,…”