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

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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.

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Acknowledgements

This study was supported in part by International Brain Research Organization/African Regional Chapter (IBRO/ARC) bursaries (2014) [M AD, MS], International Society of Neurochemistry (ISN) CAEN 1A award (2014) [MS, M AD], and Mansoura University Competitive Research Grants (2015) [SAG, HA, MS].

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Authors and Affiliations

  1. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Heba Allah Abd El Rahman, Mohamed Salama, Seham A Gad El-Hak & Mona A El-Harouny

  2. Faculty of Science, Menoufia University, Shebien, El-Koom, Egypt

    Passent ElKafrawy

  3. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Mohamed B. Abou-Donia

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  1. Heba Allah Abd El Rahman
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  2. Mohamed Salama
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  3. Seham A Gad El-Hak
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  4. Mona A El-Harouny
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  5. Passent ElKafrawy
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  6. Mohamed B. Abou-Donia
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Correspondence to Mohamed B. Abou-Donia.

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The study was approved by the Ethics Committee of Mansoura University. Participants in the current study were fully informed about details and goals of the research. Each participant signed an informed consent form declaring approval to provide blood samples, clinical data and history. For every study participant, a pseudonymous code (i.e., number combination) was created. Biological samples (i.e., blood) of each participant were only labeled with the generated code and never with personal data. The code did not contain information that can lead to the identification of the person. The code is also present in the case report form and in the consent form which contains the identifying data (first name and surname, date of birth, address, telephone number).

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El Rahman, H.A.A., Salama, M., Gad El-Hak, S.A. et al. A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity. Neurotox Res 33, 316–336 (2018). https://doi.org/10.1007/s12640-017-9793-y

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  • DOI: https://doi.org/10.1007/s12640-017-9793-y

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