A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity

Abstract

In the present study, we screened the sera of subjects chronically exposed to mixtures of pesticides (composed mainly of organophosphorus compounds (OPs) and others) and developed neurological symptoms for the presence of autoantibodies against cytoskeletal neural proteins. OPs have a well-characterized clinical profile resulting from acute cholinergic crisis. However, some of these compounds cause neuronal degeneration and demyelination known as organophosphorus compound-induced delayed neurotoxicity (OPIDN) and/or organophosphorus compound-induced chronic neurotoxicity (OPICN). Studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins against cytoskeletal neural proteins in patients with chemical-induced brain injury. In this study, we screened the serum of 50 pesticide-exposed subjects and 25 non-exposed controls, using Western blot analysis against the following proteins: neurofilament triplet proteins (NFPs), tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII), glial S100-B protein, and alpha-synuclein (SNCA). Serum reactivity was measured as arbitrary chemiluminescence units. As a group, exposed subjects had significantly higher levels of autoantibody reactivity in all cases examined. The folds of increase in of autoantibodies against neural proteins of the subjects compared to healthy humans in descending order were as follows: MBP, 7.67, MAG 5.89, CaMKII 5.50, GFAP 5.1, TAU 4.96, MAP2 4.83, SNCA 4.55, NFP 4.55, S-100B 2.43, and tubulin 1.78. This study has demonstrated the presence of serum autoantibodies to central nervous system-specific proteins in a group of farmers chronically exposed to pesticides who developed neurological signs and symptoms of neural injury. These autoantibodies can be used as future diagnostic/therapeutic target for OP-induced neurotoxicity.

RETRACTED: Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls

“…We hypothesized that exposures to chemicals present in the GW theater, such as pesticides and nerve gases, can cause CNS damage and release of CNS autoantibodies through the BBB into blood circulation, where B-lymphocytes produce antibodies to proteins and T cells produce cell-mediated immune responses, and IgG autoantibodies are then made [ 48 , 59 , 60 ]. Theoretically, IgG autoantibodies can enter through the BBB and disrupt CNS functioning, which could lead to symptoms of GWI [ 59 , 60 , 61 ]. Further research is needed to confirm this hypothesis.…”

Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson’s Disease Relative to Alzheimer’s Disease and Controls

“…Although previous reports suggested possible interaction between tau, B-amyloid, and α-syn levels ( 30 , 31 ), further studies are needed to confirm a possible contribution of α-syn in AD. The present findings support our previous studies on identification of AIAs against different cytoskeletal proteins in brain insult ( 32 , 33 ).…”

Organophosphate toxicity: updates of malathion potential toxic effects in mammals and potential treatments

“…One of these is the impairment of axonal transport by alteration of motor proteins, e.g., kinesin, or neuronal cytoskeleton proteins, such as microtubules (Naughton and Terry 2018). Another possible mechanism may involve the induction of autoimmune response in some individuals; some evidence do exist that such mechanism plays a role in other OP neurotoxic effects (El Rahman et al 2018).…”