Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease

Abstract

Type 1 diabetes mellitus results from an immune mediated or idiopathic destruction of the pancreatic beta cells. Its aetiopathogenesis remains to be elucidated, despite great progress in the characterisation of beta-cell antigens, T-lymphocyte and antibody markers as well as whole genome screening. The incidence of type 1 diabetes is rising in most countries. Moreover, a considerable proportion of patients initially presenting with type 2 diabetes mellitus have an underlying type 1 diabetes with a latent course. A proportion of type 1 diabetes patients have concomittant thyroid autoimmune disease, either Hashimoto's thyroiditis or Graves' disease. Whereas Hashimoto's thyroiditis shares the same destructive immune process as type 1 diabetes, Graves' disease is unique in stimulating specifically the TSH-receptor through high-affinity immunoglobulins. However, both the thyroid autoimmune disorders and type 1 diabetes have susceptibility genes in common, implying shared pathways of immunopathogenesis. It has become clear that the genetic composition of a host at least partly determines the course of an immune response leading either to an organ-specific autoimmune disease or creating a state of balance where antibodies are hallmarks of (auto)immunity but normal function prevails. Genetic factors including MHC ( IDDM 1-genetic locus) and non-MHC genes (IDDM 2 - IDDM X) have been shown to determine susceptibility to autoimmunity in type 1 diabetes or lifelong tolerance. Currently the importance of the various diabetes associated genes is becoming clearer due to functional studies. Our review attempts to compile the relevant data that have accumulated in recent years and offers perspectives for prediction, prevention and possibly even therapy of immune-mediated endocrinopathies.

Anti‐infectious Antibodies and Autoimmune‐associated Autoantibodies in Patients with Type I Diabetes Mellitus and their Close Family Members

“…T1DM is associated with various autoimmune disorders, 38,39 among them autoimmune thyroid diseases, 40 Addison's disease, 41 and pernicious anemia 42 . In our study we tested the sera for a wide panel of auto‐antibodies associated with various autoimmune conditions.…”

Toxicology of Autoimmune Diseases

“…Commonly targeted tissues or cells include the thyroid (thyroiditis), the β cells of the islets of Langerhans (diabetes), gastric parietal cells (gastritis), liver (autoimmune hepatitis) and steroid-producing cells in the adrenal and ovary (Addison’s disease) [3]. Susceptibility to these diseases are influenced in large part by genetics, particularly MHC-related genes [4], but they may also be influenced by environmental agents [3]. A number of toxicants have been identified that induce organ-specific autoimmune disease.…”

Autoimmune Models*

“…Target tissues include the thyroid (thyroiditis), the islets of Langerhans (diabetes), gastric parietal cells (gastritis), and steroid-producing cells in the adrenal and ovary (Addison's disease) (Lam-Tse et al 2002). These diseases are determined by a variety of separate genes, particularly MHCrelated genes (Badenhoop and Boehm 2004), but they may also be influenced by environmental agents (Lam-Tse et al 2002).…”