Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future.

Area of Science:

• Endocrinology
• Immunology
• Autoimmunity

Background:

• Thyroid autoimmunity, including Graves' hyperthyroidism and Hashimoto's thyroiditis, lacks definitive cures despite existing therapies.
• Current research often focuses on immune cells rather than the specific thyroid autoantigens driving the disease.
• The thyroid-stimulating hormone receptor (TSHR) is a key autoantigen in Graves' disease.

Purpose of the Study:

• To provide a personal perspective on thyroid autoimmunity research, emphasizing the role of autoantigens.
• To highlight the TSHR as a critical factor in Graves' disease pathogenesis.
• To underscore the need for immunotherapy and antigen-specific approaches for a cure.

Main Methods:

• Review of 40 years of research in thyroid autoimmunity.
• Analysis of the TSHR's unique structure and its role as an antigen.
• Discussion of animal models for studying thyroid autoimmunity and autoantibodies.
• Consideration of B cell autoantibodies as antigen receptors.

Main Results:

• The extracellular A-subunit of the TSHR, not the holoreceptor, is likely the primary antigen driving thyroid-stimulating autoantibodies (TSAb) in Graves' disease.
• Animal models exist for inducing or spontaneously developing TSAb.
• B cell autoantibodies play a crucial role in antigen processing and presentation.

Conclusions:

• A cure for thyroid autoimmunity necessitates a deeper understanding of thyroid autoantigens, particularly the TSHR.
• Immunotherapy targeting specific autoantigens is essential for achieving a cure.
• Available animal models and recombinant antibodies offer avenues for future research into antigen-specific immunotherapies.