The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto

Abstract

Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417–427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a ‘Swiss cheese’ model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up – like the holes in slices of cheese – to allow the catastrophic event of autoimmune destruction to occur.

Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered?

“…Finally, the presence of TAI goes far beyond the association with iron levels and that it has a complex immunopathogenesis, in which familial (genetic) and environmental factors play an important role (26).…”

Selenium and thyroid health in NZ European women

“…Hashimoto's thyroiditis is part of the spectrum of autoimmune thyroid diseases which cluster in families [53]. It displays an organized lymphocytic infiltration that leads to thyrocytes apoptosis, and to thyroid fibrosis with age [54].…”

Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto’s disease

“…Therefore, IL-10 has been confirmed to play both immunoprotective and immunodestructive roles in diabetes [32]. Because the target tissues of HD and autoimmune diabetes have been shown to be destroyed by cytotoxic T cells [1][2][3], we hypothesized that local production of IL-10 may accelerate the cytotoxic activity of T cells in the thyroid glands of HD patients and that once thyroid-specific autoimmune destruction occurs, lower expression of let-7e may cause higher production of IL-10 and induce greater destruction of the thyroid glands in patients with severe HD.…”