[Frontiers in Bioscience 16, 783-802, January 1, 2011]

Thyroperoxidase, thyroglobulin, Na+/I- symporter, pendrin in thyroid autoimmunity

Barbara Czarnocka1

1Medical Center of Postgraduate Education, Department of Biochemistry and Molecular Biology, 99/103 Marymoncka Street, 01-813 Warsaw, Poland

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Thyroid autoantigens in autoimmune thyroid disorders
3.1. Thyroperoxidase (TPO)
3.1.1. TPO protein structure and function
3.1.2. TPO as autoantigen
3.1.3. TPO immunodominant domains
3.2. Thyroglobulin (Tg)
3.2.1. Tg protein structure and function
3.2.2. Tg autoantibodies
3.2.3. T cell epitopes
3.3. Na+/I- symporter (Sodium-iodide symporter, NIS)
3.3.1. NIS protein structure and function
3.3.2. NIS antibodies
3.4. Pendrin
3.4.1. Pendrin protein structureand function
4. Summary and conclusion
5. Acknowledgement
6. References

1. ABSTRACT

The autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT) are most common endocrine disorders in humans. Both disorders are characterized by lymphocytic infiltration of the thyroid gland and the production of autoantibodies (aAb) against proteins that are thyroid-specific or expressed predominantly in the thyroid. The three main autoantigens are thyroperoxidase (TPO), thyroglobulin (Tg), and thyrotropin hormone receptor. Recently, the thyroidal iodide transporters Na+/I- symporter (NIS) and pendrin have also been identified as novel antigens in AITD. TPO-aAb and Tg-aAb are hallmarks of AITD, whereas the pathological and clinical relevance of NIS and pendrin aAb are still uncertain. To gain a greater understanding of the pathogenic mechanism(s) of autoimmune thyroid diseases at the molecular level, further characterisation of the autoantigens is required in order to shed light on why and how these molecules are seen by the immune system. This review summarizes current knowledge regarding the patho-physiological function and immunogenic response to the proteins TPO, Tg, NIS, and pendrin.