Case Report of Neuron-Binding IgGs in ALS Patient Serum in Argentina

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder characterized by ongoing loss of motoneurons. The etiology of the sporadic ALS formit is thought to be related to immune-mediated motoneuron degeneration and death. The present study was designed to describe the effect of serumfactors derived from sporadic ALS patients on mouse spinal cord preparations in vitro. Sera from patients with sporadic ALS were collected and usedfor immunofluorescence analysis to investigate their effects on neuronal survival and microgliosis. Our experiments demonstrated that 5 h applicationof serum factors (derived from three ALS patients) labeled with human IgG secondary antibody were localized to ventral spinal neurons identified withthe NeuN marker. Moreover, a significant reduction in the number of ventral NeuN positive cells was observed with serum from a patient who sufferedfrom upper motor neuron signs as criteria for ALS diagnosis (20% less compared to sham, spinal cord preparations without serum). No change inmicroglia number was found after exposure to ALS sera, although in two cases a significant decrease in microglial branch length was observed (28-32%).Microglia morphology showed increased number of end points and branches with serum from the patient with upper motor neuron symptoms. Theseobservations were absent after control sera. Our data indicate that spinal cord cultures can be a useful model to further characterize the pathologicalprocesses of sporadic ALS and the immune mechanism as previously suggested in vivo. Future studies are needed to unveil the molecular mechanismsunderlying this preferential targeting of neurons and microglia by ALS serum.