Autoantibody and environmental damage to the brain

Abstract

Behavioral abnormalities and cognitive dysfunction may be present in patients with autoimmune diseases. The mechanisms that responsible for these neuropsychiatric manifestations are still largely unknown, however several pathogenic pathways have been identified such as antibody damage, cytokine-induced neurotoxicity, as well as external factors like toxics, and medications. To further investigate some of these mechanisms we evaluated the effect of autoantibodies in animal models of neuropsychiatric systemic lupus erythematosus and narcolepsy, and the effect of the human papillomavirus vaccine in naïve mice.

Using the passive immunization method through intracerebro-ventricular injection of the antibodies, we demonstrated histological and behavioral changes. Mice immunized with 16/6 idiotypic antibodies developed cognitive impairments while those immunized with anti-ribosomal-P antibodies developed depression. The mice that received total IgG from narcoleptic patients developed sleep disturbances and brain histological changes. Further analyses of the role of the human anti-ribosomal-P autoantibody revealed that it can cross-react with the neuronal protein Gap43, interfering with cellular processes.

Immunization with the human papillomavirus vaccine induced the production of brain antibodies. Moreover, the mice immunized with the vaccine or with its adjuvant developed cognitive and behavioral deficiencies, which were ameliorated with dietary phospholipid supplementation.

Overall, herein we demonstrate that the behavioral and cognitive abnormalities can be part of the wide spectrum of clinical autoimmune manifestations. In addition, they can be caused by collateral damage due to the immune dysregulation caused by autoimmune conditions as well as by vaccination. We also suggest that different autoantibodies cause different symptoms based on different interactions with brain tissue.