Identification of IgG4-Related Disease in the English Cocker Spaniel and Dogs of Other Breeds
27th ECVIM-CA Congress, 2017
M.F. Coddou1; F. Constantino-Casas1; B. Blacklaws1; T. Scase2; M.J. Day3; P.J. Watson1
1University of Cambridge, Cambridge, UK; 2Bridge Pathology Ltd., Bristol, UK; 3School of Veterinary Sciences, University of Bristol, Bristol, UK

Chronic pancreatitis (CP) is common in the English Cocker Spaniel (ECS), and is characterised histologically by duct destruction, interlobular fibrosis and dense periductular and perivenous lymphocytic aggregates. These changes are characteristic of human autoimmune pancreatitis type 1, part of a steroid-responsive, multi-organ syndrome, newly recognised as IgG4-Related Disease (IgG4-RD). Human IgG4-RD affects one or several organs, often showing a predominance of IgG4+ plasma cells histologically, with an IgG4+/total IgG+ plasma cell ratio >40%.

This study investigated whether ECSs with CP and inflammatory disease in several organs show an increase in IgG4+ plasma cells within affected tissues. Histological sections of pancreas (n=12), liver (n=10), kidney (n=12), salivary gland (n=4), anal sacs (n=9), and conjunctiva (n=2) were obtained from 37 ECSs with idiopathic chronic inflammatory disease affecting those tissues. Control samples were identified from 18 age-matched dogs of other breeds with chronic pancreatitis (n=6), chronic idiopathic hepatitis (n=2), chronic nephritis (n=6), anal sacculitis (n=5), chronic sialadenitis (n=2) or chronic conjunctivitis (n=1). Eleven ECSs and 6 control dogs presented with disease in more than one organ. Immunohistochemistry was performed for canine total IgG and IgG subclasses (IgG2, IgG3, and IgG4). Normal tissue sections were labelled as controls. The number of plasma cells was counted in three high power fields (400x). The number of IgG4+ cells and the percentage of total IgG+ plasma cells were compared between groups using Mann-Whitney U tests.

Nineteen sections from 17 ECSs and 11 sections from 10 controls showed elevated numbers of IgG4+ plasma cells and IgG4+/IgG+ ratios >40%. Individual dogs (ECSs and other breeds) showed marked increases in IgG4+ cells. There were no significant differences in numbers of IgG4+ plasma cells between ECSs and controls for affected pancreas, liver, anal sacs, salivary glands and conjunctiva. Anal sacs showed high numbers of total IgG and IgG4+ plasma cells. Kidney sections had more IgG4+ cells in both cases and controls than other organs. Dogs of other breeds had significantly more IgG4+ plasma cells in affected kidneys.

In conclusion, several ECSs and dogs of other breeds fulfilled the histological criteria for diagnosis of IgG4-RD, supporting the existence of a multi-organ immune-mediated disease in ECS and some other dogs. Strict inclusion criteria for controls with multi-organ inflammatory disease likely selected for dogs of other breeds with IgG4-RD. Anal sacculitis showed histological changes suggesting an immune-mediated aetiology. Future studies will focus on the immunology and treatment of the disease.

Disclosures

Disclosures to report.
This study was financially supported by the Kennel Club Charitable Trust and the Cocker Spaniel Club.

  

Speaker Information
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M.F. Coddou
University of Cambridge
Cambridge, UK


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