Neuroimmunotoxicology: Humoral assessment of neurotoxicity and autoimmune mechanisms

The interactions between the nervous and immune systems have been recognize d in the development of neurodegenerative disease. This can be exploited th rough detection of the immune response to autoantigens in assessing the neu rotoxicity of environmental chemicals. To test this hypothesis. the followi ng questions were addressed. a) Are autoantibodies to nervous system (NS) a ntigens detected in populations exposed to environmental or occupational ch emicals? In sera of male workers exposed to lead or mercury, autoantibodies , primarily IgG. to neuronal cytoskeletal proteins, neurofilaments (NFs). a nd myelin basic protein (MBP) were prevalent. These findings were confirmed in mice and rats exposed to either metal. b) Do autoantibodies to NS antig ens relate to indices of exposure? In humans exposed to either metal, and s imilarly in exposed rats, titers of IgG against NFs and MBP significantly c orrelated with blood lead or urinary mercury the typical indices of exposur e. c) Do autoantibodies correlate with sensorimotor deficits? In workers ex posed to lead or mercury, a significant correlation was observed between Ig G titers and subclinical deficits. Doses of metals used in rat exposures we re subclinical. suggesting that autoantibodies may be predictive of neuroto xicity. d) Is the detection indicative of nervous system pathology? In rats exposed to metals, histopathology indicated central nervous system (CNS) a nd peripheral nervous system (PNS) damage. In addition there was evidence o f astrogliosis, which is indicative of neuronal damage in the CNS. and the presence of IgG concentrated along the blood-brain barrier, as indicated by immunostaining for antibodies. e) Are immune responses to NS antigens path ogenic? Immunoglobulin fractions from rat and human sera interfered with ne uromuscular function. These studies suggest that the detection of autoantib odies to NS-specific antigens may be used to monitor the development of neu rotoxicity to environmental chemicals and that immune mechanisms may be inv olved in the progression of neurodegeneration.