Immunogenetics of Graves' disease - An overview

Autoimmune thyroiditis, considered the prototype autoimmune organ-specific disease, was the first disease described with so called organ-specific autoantibodies. Graves' disease (GD) as a, member of this group, is characterized not only by its association with other organ-specific autoimmune diseases but also by a female preponderance, association with HLA-alleles, lymphocytic infiltration of the target organ, and tile evidence of immune system activation, particularly during the active phase of disease when autoantibodies and activated T-cells are present in the circulation. The clinical manifestation of GD by the signs and symptoms of thyrotoxicosis is due to the presence of TSH-receptor stimulating autoantibodies, thus leading to stimulation of thyroid function. GD is characterised by a heterogeneous clinical presentation, i.e. presence or absence of endocrine ophthalmopathy. Studies of association between clinical features of GD with markers within the HLA-lacus were a component of the recent 12th International Histocompatibility Workshop and Conference. Through this international collaboration more than five hundred patients with GD were analysed, The major aim was to determine whether some particular HLA markers may discriminate different forms of the disease. A genetic predisposition has been recognised in case-control-studies and in family-studies. Numerous subsequent studies have shown association of GD with genetic markers mainly within the HLA-locus. The following article is divided into two parts, the first part gives an overview of the clinical and immunological characteristics of GD, while the second part summarises at least partially the results of the International Histocompatibility Workshop GD study, respectively.