Reumatologia - oftalmopatia di Graves

Pathogenesis of Hashimoto's (lymphocytic) thyroiditis and Graves' disease

IL-6, IL-5, IL-2 thyroid autoantibodies complement-fixing, IL-1, ICAM-1, HLA class II, IFN^ϒ, HLA class I, ADCC, cell surface antigen(s), blocking antibodies(?), cellular cytotoxicity, environmental factors?

IL-6, IL-5, IL-2 thyroid autoantibodies, ADCC, complement-fixing thyroid cell, IL-1, ICAM-1, HLA class II, IFN γ, HLA class I, cell surface antigen(s), blocking antibodies(?), IL-1, UV, IL-2, cellular cytotoxicity, environmental factors?

Alteration of immune system

CD4⁺CD25⁺ T reg, defective immunological tolerance, changes in thyroid microenvironment, Th1 cytokine ↑, Th2 cytokine ↑, apoptosis of thyrocytes but not infiltrating lymphocytes, apoptosis of infiltrating lymphocytes but not thyrocytes, destruction of thyrocytes, proliferation of thyrocytes.

HT, GD_{FIG. 1}

Models of autoimmune hypothyroidism

Classical model

• CD4 T cell or CD8 T cell
• FasL–Fas ligation
• CD8 T cell
• Release of cytotoxic granules

Immune-mediated apoptosis and cytotoxic death of thyrocytes, loss of thyroid follicles, clinical hypothyroidism.

Nonclassical model

• Thyrocytes
• IFNγ, TNFα
• Presence of inflammatory factors, for example, released by macrophages and lymphocytes

Immune-mediated chronic inhibition of thyroid function, thyroid atrophy, clinical hypothyroidism.

Thyroid gland

• Thyroid follicular endothelial cell
• Thyrotropin receptor
• Thyrotropin-receptor peptides
• MHC class II, CD40, CD154
• T-cell receptor
• Helper T cell
• TNF, Interferon-γ
• B cell, Interferon-γ, Interleukin-2
• Anti-thyrotropin-receptor antibody
• Expanded orbital tissues
• Orbital fibroblast
• Hyperplastic thyroid follicle, T3, T4