Neurodegenerative and inflammatory mechanisms induced by serum IgG from ALS patients

GIULIANA C DI MAURO; BRUNO DE AMBROSI; OSVALDO D UCHITEL; GRACIELA L MAZZONE

Córdoba

Simposio; Frontiers in Bioscience 3; 2018

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects the skeletal musculature, so that individuals suffering from it suffer a progressive paralysis that leads to death between 2 to 5 years after diagnosis. It has not yet been discovered a cure for this disease, and drugs approved for treatment only prolong life in a few months. Approximately 10% of cases are due to genetic causes, while the remaining 90% due to sporadic causes. For genetic cases, several genes involved in the pathology have been identified, such as the mutation of the C9ORF gene. With respect to the sporadic form, there is no mechanism identified as a trigger, although one of the hypotheses is autoimmunity. Immunoglobulins (IgG) from patients with sporadic ALS would be responsible for neurodegeneration and, in addition, an inflammatory process. Previous laboratory work, using mice models, showed the binding of these IgG to cells of the neuromuscular plate and to motor neurons of the brainstem. In this context, in the present work we try to identify the cellular events triggered by the application of sera from patients with ALS on ex vivo cultures of mouse spinal cord, using immunofluorescence and RT-PCR. Special attention was paid to the neurons of those tissues, and to the microglia, a cell type related to inflammation. In agreement with previous results of the laboratory, it was seen that the IgG of the patients bind to a population neurons of the spinal cord. In turn, some of the used sera cause a neuronal reduction, and also a microglial activation. Despite the diversity among the different patients, the conclusions of this work support the hypothesis of autoimmunity involved in the development of the disease.