Hashimoto's Thyroiditis: From Genes to the Disease

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease.
• It involves lymphocytic infiltration and gradual thyroid destruction, potentially causing hypothyroidism.
• Key biochemical markers include thyroid peroxidase and thyroglobulin autoantibodies, more prevalent in females and increasing with age.

Purpose of the Study:

• To review the known genetic and environmental factors contributing to Hashimoto's thyroiditis.
• To explore the immunological mechanisms underlying thyroid autoimmunity in HT.
• To understand the role of various endogenous and exogenous factors in HT pathogenesis.

Main Methods:

• Review of family and twin studies confirming genetic susceptibility.
• Analysis of gene associations (HLA, CTLA-4, PTPN22, etc.) with HT occurrence and severity.
• Examination of endogenous factors (sex, pregnancy, microchimerism) and environmental factors (iodine, drugs, infections).

Main Results:

• Strong genetic predisposition to HT is established.
• Female sex, pregnancy, and fetal microchimerism are significant endogenous factors.
• Environmental influences include iodine intake, drugs, infections, and chemicals.
• Immune responses involve disturbed self-tolerance, antigen presentation, and T-cell mediated cytotoxicity (Th1 and Th17 responses).

Conclusions:

• HT pathogenesis is multifactorial, involving complex interactions between genetic susceptibility and environmental triggers.
• Immune system dysregulation, particularly T-cell responses, is central to thyroid destruction.
• Further research is needed to fully elucidate the intricate mechanisms of HT aetiology and pathogenesis.