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Cross-Reactivity between Chemical Antibodies Formed to Serum Proteins and Thyroid Axis Target Sites

1
Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
2
Massachusetts General Hospital, Charlestown, MA 02129, USA
3
Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
4
Immunosciences Laboratory, Inc., Los Angeles, CA 90035, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7324; https://doi.org/10.3390/ijms21197324
Received: 12 May 2020 / Revised: 29 September 2020 / Accepted: 2 October 2020 / Published: 3 October 2020
(This article belongs to the Section Molecular Immunology)
In some instances, when chemicals bind to proteins, they have the potential to induce a conformational change in the macromolecule that may misfold in such a way that makes it similar to the various target sites or act as a neoantigen without conformational change. Cross-reactivity then can occur if epitopes of the protein share surface topology to similar binding sites. Alteration of peptides that share topological equivalence with alternating side chains can lead to the formation of binding surfaces that may mimic the antigenic structure of a variant peptide or protein. We investigated how antibodies made against thyroid target sites may bind to various chemical–albumin compounds where binding of the chemical has induced human serum albumin (HSA) misfolding. We found that specific monoclonal or polyclonal antibodies developed against thyroid-stimulating hormone (TSH) receptor, 5′-deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin (TBG), thyroxine (T4), and triiodothyronine (T3) bound to various chemical HSA compounds. Our study identified a new mechanism through which chemicals bound to circulating serum proteins lead to structural protein misfolding that creates neoantigens, resulting in the development of antibodies that bind to key target proteins of the thyroid axis through protein misfolding. For demonstration of specificity of thyroid antibody binding to various haptenic chemicals bound to HSA, both serial dilution and inhibition studies were performed and proportioned to the dilution. A significant decline in these reactions was observed. This laboratory analysis of immune reactivity between thyroid target sites and chemicals bound to HSA antibodies identifies a new mechanism by which chemicals can disrupt thyroid function. View Full-Text
Keywords: hapten; neoantigen; cross-reactivity; thyroid; chemicals hapten; neoantigen; cross-reactivity; thyroid; chemicals
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Kharrazian, D.; Herbert, M.; Vojdani, A. Cross-Reactivity between Chemical Antibodies Formed to Serum Proteins and Thyroid Axis Target Sites. Int. J. Mol. Sci. 2020, 21, 7324.

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