Assessment of glial fibrillary acidic protein and anti‐glial fibrillary acidic protein autoantibody concentrations and necrotising meningoencephalitis risk genotype in dogs with pug dog myelopathy

Abstract

BackgroundPugs commonly present with thoracolumbar myelopathy, also known as pug dog myelopathy (PDM), which is clinically characterised by progressive signs involving the pelvic limbs, no apparent signs of pain and, often, incontinence. In addition to meningeal fibrosis and focal spinal cord destruction, histopathology has confirmed lymphohistiocytic infiltrates in the central nervous system (CNS) in a considerable number of pugs with PDM. Lymphohistiocytic CNS inflammation also characterises necrotising meningoencephalitis (NME) in pugs. This study aimed to investigate the potential contribution of an immunological aetiology to the development of PDM.MethodsThe concentrations of glial fibrillary acidic protein (GFAP) in serum and CSF and of anti‐GFAP autoantibodies in CSF were measured with an ELISA. In addition, a commercial test was used for genetic characterisation of the dog leukocyte antigen class II haplotype, which is associated with NME susceptibility.ResultsThis study included 87 dogs: 52 PDM pugs, 14 control pugs, four NME pugs and 17 dogs of breeds other than pugs that were investigated for neurological disease (neuro controls). Anti‐GFAP autoantibodies were present in 15 of 19 (79%) of the PDM pugs tested versus six of 16 (38%) of the neuro controls tested (p = 0.018). All 18 PDM pugs evaluated had detectable CSF GFAP. Serum GFAP was detected in two of three (67%) of the NME pugs and in two of 11 (18%) of the control pugs but not in any of the 40 tested PDM pugs. Male pugs heterozygous for the NME risk haplotype had an earlier onset of clinical signs (70 months) compared to male pugs without the risk haplotype (78 months) (p = 0.036).LimitationsThe study was limited by the lack of healthy dogs of breeds other than pugs and the small numbers of control pugs and pugs with NME.ConclusionsThe high proportion of PDM pugs with anti‐GFAP autoantibodies and high CSF GFAP concentrations provide support for a potential immunological contribution to the development of PDM.

Pug thoracolumbar myelopathy: vertebral instability, immune‐mediated disorder or a combination of factors?

“…As Rohdin and colleagues suggest, 3,11 it is even possible that hypoxia, similar to observations in human medicine, 17 associated with the brachycephalic conformation has a role to play in the development of spinal disorders in pugs.…”

“…In a new study, summarised on p 478 of this issue of Vet Record, Rohdin and colleagues explore further the possibility of an immunological aetiology in pugs with thoracolumbar myelopathy. 11 They have done this by assessing serum and cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and CSF anti-GFAP autoantibody concentrations in four groups of dogs: pugs with thoracolumbar myelopathy confirmed by MRI; neurologically normal pugs older than six-years-old; pugs diagnosed with NME; and dogs of breeds other than pugs with a variation of diagnosed neurological disorders.…”

“…However, not all pugs with thoracolumbar myelopathy had increased CSF GFAP or high CSF anti-GFAP auto-antibodies. Rohdin and colleagues 11 explained this by postulating that increased GFAP might only be present in the acute stage of the disease. Similarly, in their previous study, 9 CNS cellular infiltrates were predominantly found in dogs with a short duration of clinical signs.…”

“…9 As the disease becomes chronic, the concentrations of GFAP would return to normal, while anti-GFAP autoantibody concentrations remain high. 11 So, is 'pug dog myelopathy' an autoimmune disorder? The pathophysiology of this enigmatic disorder might unfortunately be too complex to answer this question with a simple 'yes' or 'no'.…”