[Frontiers in Bioscience, Landmark, 25, 912-929, Jan 1, 2020]

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

Roberto Bei1, Gerald J. Mizejewski2

1Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy, 2Division 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

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Autoantigens and autoimmunity
4. Disordered self-proteins and autoimmunity
5. Is AFP a disordered protein?
6. Spontaneous immune response to AFP in hepatocellular cancer (HCC) patients
7. Batten disease and AFP autoantibodies
8. Conclusion
9. Acknowledgement
10. References

1. 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.

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Key Words: Alpha-fetoprotein, Autoimmunity, Antigens, Epitopes, Disordered Protein, Autoimmune Disorders, Batten Disease, Review

Send correspondence to: Roberto Bei, Dept. of Clinical Sciences and Translational Medicine, Faculty of Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy, Tel: 39 06-72596522, Fax: 39 06-72596506, E-mail: bei@med.uniroma2.it