Expression of platelet-derived growth factor receptor-alpha/beta, vascular endothelial growth factor receptor-2, c-Abl, and c-Kit in canine granulomatous meningoencephalitis and necrotizing encephalitis

Abstract

Background: Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that granulomatous meningoencephalomyelitis (GME) and necrotizing encephalomyelitis (NE) are similar to multiple sclerosis (MS), which is a human autoimmune demyelinating central nervous system disease. Objectives: Considering this perspective, we hypothesized that canine GME and NE have significant expression of one or more TKs, which are associated with human MS pathogenesis. Methods: To determine the possible use of conventional multi-targeted TKIs as a treatment for canine GME and NE, we characterized the immunohistochemical expression of platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-ss, vascular endothelial growth factor receptor (VEGFR)-2, c-Abl and c-Kit in GME and NE samples. Results: Histological samples from four dogs with GME and three with NE were retrieved. All samples stained positive for PDGFR-ss (7/7 [100%]). PDGFR-alpha and c-Kit were expressed in 3/7 (42.8%) samples each. c-Abl was identified in 2/7 (28.5%) samples; no sample showed VEGFR-2 (0%) expression. Co-expression of TKs was identified in 6/7 (85.7%) dogs. Conclusions All samples were positive for at least one or more of PDGFR-alpha, PDGFR-ss, c-Kit and c-Abl, which are known as the target TKs of conventional multi-targeted TKIs. Their presence does suggest that these TKs may play a role in the pathogenesis of GME and NE. Therefore, multi-targeted TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs.