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. 2015 Apr;35(4):383-97.
doi: 10.1002/jat.3031. Epub 2014 Jul 18.

Elevated levels of antibodies against xenobiotics in a subgroup of healthy subjects

Aristo Vojdani  1 , Datis Kharrazian, Partha Sarathi Mukherjee
Affiliations

Elevated levels of antibodies against xenobiotics in a subgroup of healthy subjects

Aristo Vojdani et al. J Appl Toxicol. 2015 Apr.

Erratum in

  • J Appl Toxicol. 2016 May;36(5):748

Abstract

In spite of numerous research efforts, the exact etiology of autoimmune diseases remains largely unknown. Genetics and environmental factors, including xenobiotics, are believed to be involved in the induction of autoimmune disease. Some environmental chemicals, acting as haptens, can bind to a high-molecular-weight carrier protein such as human serum albumin (HSA), causing the immune system to misidentify self-tissue as an invader and launch an immune response against it, leading to autoimmunity. This study aimed to examine the percentage of blood samples from healthy donors in which chemical agents mounted immune challenges and produced antibodies against HSA-bound chemicals. The levels of specific antibodies against 12 different chemicals bound to HSA were measured by ELISA in serum from 400 blood donors. We found that 10% (IgG) and 17% (IgM) of tested individuals showed significant antibody elevation against aflatoxin-HSA adduct. The percentage of elevation against the other 11 chemicals ranged from 8% to 22% (IgG) and 13% to 18% (IgM). Performance of serial dilution and inhibition of the chemical-antibody reaction by specific antigens but not by non-specific antigens were indicative of the specificity of these antibodies. Although we lack information about chemical exposure in the tested individuals, detection of antibodies against various protein adducts may indicate chronic exposure to these chemical haptens in about 20% of the tested individuals. Currently the pathological significance of these antibodies in human blood is still unclear, and this protein adduct formation could be one of the mechanisms by which environmental chemicals induce autoimmune reactivity in a significant percentage of the population.

Keywords: adducts; autoimmunity; chemicals; haptens; xenobiotics.

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Figures

Figure 1
Figure 1
Results for chemical antibodies expressed as optical density (OD) at 405 nm in the form of scattergrams. (A) Aflatoxin IgG. (B) Aflatoxin IgM. (C) Formaldehyde IgG. (D) Formaldehyde IgM. (E) Isocyanates IgG. (F) Isocyanates IgM. (G) Trimellitic & Phthalic Anhydride IgG. (H) Trimellitic & Phthalic Anhydride IgM.
Figure 2
Figure 2
Results for chemical antibodies expressed as optical density (OD) at 405 nm in the form of scattergrams. (A) Benzenes IgG. (B) Benzenes IgM. (C) Bisphenol-A IgG. (D) Bisphenol-A IgM. (E) Tetrabromobisphenol-A IgG. (F) Tetrabromobisphenol-A IgM. (G) Tetrachloroethylene IgG. (H) Tetrachloroethylene IgM.
Figure 3
Figure 3
Results for chemical antibodies expressed as optical density (OD) at 405 nm in the form of scattergrams. (A) Parabens IgG. (B) Parabens IgM. (C) Mercury IgG. (D) Mercury IgM. (E) Mixed Heavy Metals IgG. (F) Mixed Heavy Metals IgM. (G) Pyrethroids IgG. (H) Pyrethroids IgM.
Figure 4
Figure 4
Serial dilutions for chemical antibodies expressed as optical density (OD) at 405 nm in the form of curves. (A) Aflatoxin IgG & IgM. (B) Formaldehyde IgG & IgM. (C) Isocyanates IgG & IgM. (D) Trimellitic Anhydride IgG & IgM. (E) Benzene Ring Compounds IgG & IgM. (F) Bisphenol-A IgG & IgM.
Figure 5
Figure 5
Serial dilutions for chemical antibodies expressed as optical density (OD) at 405 nm in the form of curves. (A) Tetrabromobisphenol-A IgG & IgM. (B) Tetrachloroethylene IgG & IgM. (C) Mercury Compounds IgG & IgM. (D) Mixed Heavy Metals IgG & IgM. (E) Parabens IgG & IgM. (F) Pyrethroids IgG & IgM.
Figure 6
Figure 6
Scatterplot matrix of the optical density (OD) of the IgG antibody levels against the haptenic chemicals.
Figure 7
Figure 7
Scatterplot matrix of the optical density (OD) of the IgM antibody levels against the haptenic chemicals.
Figure 8
Figure 8
Two-way cluster analysis of the Pearson's correlation coefficients between all pairs of the optical density (OD) of the antibody levels (both IgG and IgM).
Figure 9
Figure 9
Simplified schematic for the metabolism of chemical compounds.
See this image and copyright information in PMC

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