Abstract
Introduction There has been recent interest in excitotoxicity as a contributor to neuronal cell death and progression in MS. Histopathology studies imply a specific loss of inhibitory interneurons in the cortex of MS patients, and CSF parvalbumin (exclusive to interneurons) is associated with progression. We investigated MS sera for interneuron antibodies.
Methods Serum from 103 patients with MS was analysed using indirect immunofluorescence on paraformaldehyde fixed frozen rat brain. The cerebellum, brainstem and cortex were viewed using deconvolution microscopy. Neurons were identified by counterstaining with neurofilament, parvalbumin and by morphology.
Results Ten of 103 (9.7%) patients exhibited high titre (>1:640) antibodies against interneurons. The IgG binding pattern was the same in all patients – vesicular intracellular components of basket cells, golgi cells, stellate cells and bipolar interneurons in the cortex and brainstem. Co-binding studies with parvalbumin confirmed inhibitory interneurons as the target and affiliated binding to the renal principal cell, indicated the IgG specificity was the same in positive patients. The female to male ratio was 4:1. The median age was 44 years at the time of antibody detection. At that point there was not a significant difference in EDSS, distribution of lesions or type of MS between antibody positive and negative patients. We will provide 10-year follow up data on the outcomes of these patients in this paper.
Conclusions 10% of patients with MS have inhibitory interneuron antibodies in the blood and work is required to determine whether this leads to neuronal cell loss and cerebral atrophy in MS.
