The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies.

Datis Kharrazian,Martha Herbert,Aristo Vojdani

doi:10.3390/toxics7020026

Abstract

Patients with Parkinson’s disease (PD) have increased susceptibility to bisphenol A (BPA) exposure since they have an impaired biotransformation capacity to metabolize BPA. PD subjects have reduced levels of conjugated BPA compared to controls. Reduced ability to conjugate BPA provides increased opportunity for unconjugated BPA to bind to albumin in human serum and protein disulfide isomerase on neurons. Once unconjugated BPA binds to proteins, it changes the allosteric structure of the newly configured protein leading to protein misfolding and the ability of the newly configured protein to act as a neoantigen. Once this neoantigen is formed, the immune system produces antibodies against it. The goal of our research was to investigate associations between unconjugated BPA bound to human serum albumin (BPA–HSA) antibodies and alpha-synuclein antibodies and between Protein Disulfide Isomerase (PDI) antibodies and alpha-synuclein antibodies. Enzyme–linked immunosorbent assay was used to determine the occurrences of alpha-synuclein antibodies, antibodies to BPA–HSA adducts, and PDI antibodies in the sera of blood donors. Subjects that exhibited high levels of unconjugated BPA–HSA antibodies or PDI antibodies had correlations and substantial risk for also exhibiting high levels of alpha-synuclein antibodies (p < 0.0001). We conclude that there are significant associations and risks between antibodies to BPA–HSA adducts and PDI antibodies for developing alpha-synuclein antibodies.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and 95% of cases are sporadic and unassociated with familial PD [1]
Measurements for IgG, IgM, and IgA were measured for both bisphenol A (BPA)–HSA and Protein Disulfide Isomerase (PDI)
There was a significant difference in the optical density means for those subjects that were above the mean OD compared to subjects that were below the mean OD in all tested groups (p-value < 0.0001)

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and 95% of cases are sporadic and unassociated with familial PD [1]. Environmental risk factors leading to PD is a vital area of investigation. The specific mechanisms of how environmental chemicals promote the development of PD are an area of ongoing research. Epidemiological, animal, and human research suggest that the development of alpha-synuclein aggregates is a key feature of PD [1]. The mechanisms of how environmental chemicals lead to the development of alpha-synuclein aggregates are important for ubiquitous environmental compounds. Bisphenol A (2,2-bis(4-hydroxyphenyl) propane; BPA) is one of the most common chemicals to which humans

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