Last update:
18-Jul-2000

Arch Hellen Med, 16(4), July-August 1999, 337-351

REVIEW

Thyroid autoimmunity
Autoantigens, autoantibodies, autoreactive T-lymphocytes, pathogenesis

P. LYMBERI,¹ G. PHILIPPOU^2
1Immunology Department, Hellenic Pasteur Institute
²1st Endocrine Section, "Alexandra" Hospital, Athens, Greece

Autoimmune thyroid disease has been the paradigm of organ-specific autoimmunity for over 30 years. The high incidence in the general population, the easy access to the target organ and the existence of well established animal models of thyroiditis have facilitated research on the pathogenesis of the disease. Thyroid autoimmune syndromes �Graves' disease, Hashimoto's thyroiditis, primary myxedema or primary hypothyroidism, and postpartum thyroiditis� are characterized by reactivity to self thyroid antigens involving autoreactive T cells and/or circulating autoantibodies. There are three distinct and well characterized thyroid autoantigens: thyroglobulin (TG), thyroid peroxidase (TPO, previously known as "microsomal antigen"), and the thyroid stimulating hormone (TSH) receptor (TSH-R). Autoantibodies to the TSH receptor are responsible for hyperthyroidism in Graves' disease, whereas antibodies to TPO and TG, in high titles, are associated with Hashimoto's disease and primary myxedema. Thyroid autoantibodies are easily measured by simple, sensitive and specific radio- and enzyme-immunoassays. The molecular cloning of genes encoding for all three thyroid autoantigens has had a major impact on the understanding of their autoantigenicity. Knowledge of their primary structures allowed the identification of linear B- and T-cell epitopes through the use of recombinant antigen fragments or synthetic peptides. In general, there is a correlation between these diseases and the genetic loci of HLA-DR and HLA-DQ (HLA class II) regions. Particularly in Caucasians, Graves' disease is related to DR3 haplotype, Hashimoto's thyroiditis to HLA-DR4, DR5 ��� DQ7, and primary myxedema with HLA-DR5 ��� DQ7. Research is supported by the development of animal models, spontaneously-developed in certain strains or artificially-induced in normal animals by administration of the relevant peptides. These thyroid-based animal models also constitute precious tools for the study of organ-specific autoimmunity.

Key words: Autoimmune thyroid disease, Autoreactive T-lymphocytes, Thyroid autoantibodies, Thyroid autoantigens.