IMR Press / FBL / Volume 25 / Issue 5 / DOI: 10.2741/4840

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review
Alpha-fetoprotein is an autoantigen in hepatocellular carcinoma and juvenile Batten disease
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1 Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
2 Division of Translational Medicine, Molecular Diagnostics, Wadsworth Center, New York State Department of Health, P.O. Box 509, Empire State Plaza, Albany, New York 12201-0509
Front. Biosci. (Landmark Ed) 2020, 25(5), 912–929; https://doi.org/10.2741/4840
Published: 1 January 2020
Abstract

Failure of immune tolerance leads to production of autoantibodies to self-antigens. The repertoire of autoantibodies detected in cancer patients can indicate the presence of autoimmune disease. Alpha-fetoprotein (AFP) autoantibodies have been found in patients with hepatocellular carcinoma (HCC) and in juvenile Batten disease (BD), a neurodegenerative condition involving autoimmunity. Variant conformational forms of AFP together with exposed occult antigenic determinant sites on the AFP polypeptide resemble the features of a disordered protein which can impair central immune tolerance. These aberrant structural protein forms can lead to the persistence of autoantibody production by immune sensitized B-lymphocytes. Thus, it is not surprising that AFP, a self-antigen, can induce autoimmune responses in humans. Herein, we discuss the molecular and antigenic properties of AFP which make it a disordered protein, and its ability to induce autoantibody production to AFP cryptic epitopes in both HHC and BD patients. Such insights might aid in the future design of AFP-based vaccines and to discovery of novel pathogenic mechanisms of autoimmune diseases which demonstrate the presence of denatured intermediate forms of AFP.

Keywords
Alpha-fetoprotein
Autoimmunity
Antigens
Epitopes
Disordered Protein
Autoimmune Disorders
Batten Disease
Review
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