Autoimmune thyroid disease: propagation and progression

Abstract

Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence. The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

Immigration and the incidence of Graves' thyrotoxicosis, thyrotoxic multinodular goiter and solitary toxic adenoma

“…Smoking is suggested to be a major risk factor in Graves' ophthalmopathy and a minor risk factor in GD (22,23). The latter fact is supported by our data because the proportion of smokers varied between the groups with different geographic origin where the lowest share of smokers was observed in the group with the highest share of GD.…”

The rationale for B lymphocyte depletion in Graves’ disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

“…Upon CD40/CD40L engagement, B7-1 or B7-2 (CD80/CD86) molecules are activated on the APC cell membrane which, upon interaction with T cell CD28 or the cytotoxic T lymphocyte antigen-4 (CTLA-4) confers an increase or a decrease respectively in T cell function, for example, by the production of cytokines, CD4 þ CD25 þ regulatory T cells or by controlling Fasmediated apoptosis (57,58). CTLA-4 gene polymorphisms may be involved in the susceptibility to GD (20,58). The importance of B cells in modulating T cell functions was shown in Takemura's RA synovium -SCID mouse chimeras, where decreases in T cell infiltration, GC size and inflammatory cytokines were seen upon B cell depletion (6).…”

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

“…Autoimmune thyroid disorder is an organspecific target (Swain et al 2005). Genetic, environmental exposures, and various endogenous factors are responsible for initiating the autoimmune thyroid disorder (Davies et al 2012;Brent 2010;Weetman 2003). It is reported that thyroid hormones (THs), triiodothyronine (T 3 ) and thyroxin (T 4 ), show the strong association between hyperthyroidism and high energy expenditure (EE) in human (Klieverik et al 2009).…”