Neuron-specific enolase antibodies in patients with sudden acquired retinal degeneration syndrome

Abstract

Sudden acquired retinal degeneration syndrome (SARDS) is a disease characterised by sudden and bilateral vision loss of dogs. Previous studies failed to identify the underlying cause [Mattson, A., Roberts, S.M., Isherwood, J.M.E., 1992. Clinical features suggesting hyperadrenocorticism associated with sudden acquired retinal degeneration syndrome in a dog. J. Am. Anim. Hosp. Assoc. 28, 199-202; Van der Woerdt, A., Nasisse, M.P., Davidson, M.G., 1991. Sudden acquired retinal degeneration in the dog: clinical and laboratory findings in 36 cases. Prog. Vet. Comp. Ophthamol. 1, 11-18] and earlier investigations about the occurrence of anti-retinal antibodies in SARDS patients showed inconsistent results. To provide a novel approach to those findings we designed a more detailed study. Autoantibodies of SARDS patients and normal controls were tested against the purified autoantigens S-antigen and cellular retinaldehyde binding protein (CRALBP) that play a role in human autoimmune uveitis. Next we tested the autoantibody binding pattern to whole retinal lysate. No difference in the incidence of autoantibodies could be found between SARDS patients and healthy controls while testing the well-known autoantigens S-antigen and CRALBP. Potential novel, yet unknown autoantigens were identified by a screening test using the retinal proteome as an autoantigenic source. In SARDS patients and normal controls, several retinal proteins were bound by IgG antibodies, but one band was strongly marked by SARDS patients. That band was excised, subjected to mass spectrometry (matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF/TOF)) and identified as neuron-specific enolase. Binding of the IgG autoantibodies of SARDS-affected dogs to this protein was verified using purified NSE, revealing 25% of NSE autoantibody-positive SARDS patients and 0% of negative controls. Our findings indicate that at least some dogs with SARDS have autoantibodies against NSE, although it is unclear whether these play a causative role in SARDS or whether they are the result of retinal destruction by another mechanism.