Neuroimmunotoxicology: Humoral Assessment of Neurotoxicity and Autoimmune Mechanisms

Abstract

The interactions between the nervous and immune systems have been recognized in the development of neurodegenerative disease. This can be exploited through detection of the immune response to autoantigens in assessing the neurotoxicity of environmental chemicals. To test this hypothesis, the following questions were addressed. a) Are autoantibodies to nervous system (NS) antigens detected in populations exposed to environmental or occupational chemicals? In sera of male workers exposed to lead or mercury, autoantibodies, primarily IgG, to neuronal cytoskeletal proteins, neurofilaments (NFs), and myelin basic protein (MBP) were prevalent. These findings were confirmed in mice and rats exposed to either metal. b) Do autoantibodies to NS antigens relate to indices of exposure? In humans exposed to either metal, and similarly in exposed rats, titers of lgG against NFs and MBP significantly correlated with blood lead or urinary mercury, the typical indices of exposure. c) Do autoantibodies correlate with sensorimotor deficits? In workers exposed to lead or mercury, a significant correlation was observed between lgG titers and subclinical deficits. Doses of metals used in rat exposures were subclinical, suggesting that autoantibodies may be predictive of neurotoxicity. d) Is the detection indicative of nervous system pathology? In rats exposed to metals, histopathology indicated central nervous system (CNS) and peripheral nervous system (PNS) damage. In addition there was evidence of astrogliosis, which is indicative of neuronal damage in the CNS, and the presence of lgG concentrated along the blood-brain barrier, as indicated by immunostaining for antibodies. e) Are immune responses to NS antigens pathogenic? Immunoglobulin fractions from rat and human sera interfered with neuromuscular function. These studies suggest that the detection of autoantibodies to NS-specific antigens may be used to monitor the development of neurotoxicity to environmental chemicals and that immune mechanisms may be involved in the progression of neurodegeneration.

Non-coplanar polychlorinated biphenyl (PCB)-induced immunotoxicity is coincident with alterations in the serotonergic system

“…This is not surprising as it has been shown that chemical-induced alterations of one biological system can affect normal functioning of another (El-Fawal et al, 1999), and this is especially true when two organ systems (e.g., the immune and nervous systems) are known to share common receptors/ligands and act to cross-regulate each other (Lawrence and Kim, 2000). In this latter scenario, a variety of immune cell types from both mammals and fish have demonstrated 5-HT receptors and the 5-HT reuptake transporter (5-HTT) (Khan and Deschaux, 1997;Lawrence and Kim, 2000).…”

Detection of Antinuclear and Antilaminin Antibodies in Autistic Children Who Received Thimerosal-Containing Vaccines

“…In contrast, the antibodies to antineurofilament 68-kd protein are virtually nonexistent in autistic children, who primarily harbor antibodies to myelin basic protein [8] but sometimes also have antibodies to glial filament protein and neuron-axonal filament 200-kd protein [11]. Furthermore, it should be clearly pointed out that the mercuryexposed industrial workers very seldom harbor antibodies to myelin basic protein or neuron-axonal filament 200-kd protein [3]. Indeed, this is an important distinction between the mercury-exposed autoimmunity and the idiopathic autoimmunity in autism.…”

“…Autistic children are not known to have the nephrotic syndrome and, as described here, they had normal titers of antilaminin antibodies, suggesting the absence of a mercury-induced autoimmune reaction in autistic children. Mercury exposure in industrial workers induces antibodies to neural antigens, mainly the neurofilament 68-kd protein [3]. In contrast, the antibodies to antineurofilament 68-kd protein are virtually nonexistent in autistic children, who primarily harbor antibodies to myelin basic protein [8] but sometimes also have antibodies to glial filament protein and neuron-axonal filament 200-kd protein [11].…”

Expression of immunoregulatory genes and its relationship to lead exposure and lead‐mediated oxidative stress in wild ungulates from an abandoned mining area

“…Lead's ability to influence the risk of autoimmunity is not always associated with a rigorous shift to T h 2 responses [35]. Some studies have described a more complicated sequence of events, in which the type-1 cytokine IFN-g is also linked with heavy metal-induced autoimmunity, which may also be associated to kidney pathologies [36].…”