# Pathologic Changes in and Immunophenotyping of Polymyositis in the Dutch Kooiker Dog

## TL;DR

This study identifies polymyositis in Kooiker dogs, a breed-specific inflammatory muscle disease involving immune responses, particularly T-cells.

## Contribution

The study characterizes polymyositis in Kooiker dogs, revealing unique immune features and contributing to understanding immune-mediated muscle diseases.

## Key findings

- Muscle biopsies showed inflammation, cell infiltration, and muscle damage with regeneration.
- T-cells were the predominant immune cell type, with involvement of both adaptive and innate immune responses.
- MHC-II expression on muscle fibers suggests a role in sustaining inflammation.

## Abstract

In 2023, we described the clinical signs and histology of an inflammatory myopathy that affects Kooiker dogs, one of the nine Dutch breeds. In this additional study, we further investigated muscle changes in the affected dogs. Our results showed typical signs of inflammation, cell infiltration into muscle tissue, and immunophenotyping that revealed the involvement of both adaptive and innate immune responses, with T-cells being the predominant cell type. Additionally, histological analysis highlighted muscle damage and regeneration. Based on our results, we conclude that this is polymyositis (PM). PM in these dogs shares similarities with other breeds but appears to have unique characteristics. The findings described contribute to understanding PM in Kooiker dogs and its immune-mediated mechanisms in general.

Earlier, we described a breed-specific inflammatory myopathy in Dutch Kooiker dogs (Het Nederlandse Kooikerhondje), one of the nine Dutch breeds. The disease commonly manifests itself with clinical signs of difficulty walking, muscle weakness, exercise intolerance, and/or dysphagia. In nearly all dogs’ creatine kinase (CK) activity was elevated. Histopathology reveals the infiltration of inflammatory cells within the skeletal muscles. The objective of this study was to further investigate and characterize the histopathological changes in muscle tissue and immunophenotype the inflammatory infiltrates. FFPE fixed-muscle biopsies from 39 purebred Kooiker dogs were included and evaluated histopathologically according to a tailored classification scheme for skeletal muscle inflammation. As in other breed-related inflammatory myopathies, multifocal, mixed, and predominantly mononuclear cell infiltration was present, with an initial invasion of viable muscle fibres and the surrounding stroma leading to inflammation, necrosis, and tissue damage. Immunophenotyping primarily revealed lymphohistiocytic infiltrates, with CD3+ T-cells being the predominant inflammatory cell type, accompanied by CD8+ cytotoxic T-cells. The concurrent expression of MHC-II class molecules on myofibres suggests their involvement in initiating and maintaining inflammation. Additionally, CD20+ B-cells were identified, though in lower numbers compared to T-cells, and IBA-1-positive macrophages were frequently seen. These findings suggest a breed-specific subtype of polymyositis in Kooiker dogs, akin to other breeds. This study sheds light on the immune response activation, combining adaptive and innate mechanisms, contributing to our understanding of polymyositis in this breed.