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Front Biosci (Landmark Ed). 2020 Jan 1;25:912-929.

Alpha-fetoprotein is an autoantigen in hepatocellular carcinoma and juvenile Batten disease.

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Department of Clinical Sciences and Translational Medicine, Faculty of Medicine, University of Rome,
Wadsworth Center, New York State Department of Health, PO Box 509, Empire State Plaza, Albany, NY, 12201-0509, USA.


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.


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