Common immune mechanism linked to opposing thyroid conditions

Graves' disease and Hashimoto's thyroiditis, while causing hyperthyroidism and hypothyroidism, respectively, may originate from the same process where the immune system eliminates mutant cells that overproduce hormones, leading to potential autoimmune responses in susceptible individuals, according to a study by Tomer Milo, Uri Alon and two others.

This theory posits that both GD and HT arise from a physiological process wherein autoreactive T cells target and eliminate cells in the thyroid that abnormally overproduce hormones. This action, although beneficial in preventing the formation of toxic nodules, comes with a significant downside.

The study delves into the mechanisms underlying these diseases, focusing on the role of autoreactive T cells. These cells are reactive to specific thyroid antigens: The thyroid-stimulating hormone (TSH) receptor in the case of GD, and thyroglobulin (Tg)/thyroid peroxidase (TPO) in HT. It is proposed that these T cells, while performing the critical function of removing hypersecreting mutant cells, inadvertently trigger a humoral response. This response, in susceptible individuals, leads to the production of antibodies that attack thyroid antigens, setting the stage for the development of GD or HT. This intricate mechanism sheds light on why individuals might develop either of these conditions.

The significance of this study lies in its potential explanation for the observed links between GD and HT. Despite their opposite effects on thyroid function, these diseases share similar risk factors and incidence patterns. Moreover, it's observed that these conditions can sometimes interconvert, further complicating their clinical picture. The autoimmune surveillance theory, by proposing a shared etiological root, offers a compelling rationale for these connections. Understanding this underlying mechanism not only bridges the gap in knowledge about these diseases but also opens avenues for targeted therapeutic interventions in the future.

Elsevier Ltd: Tomer Milo, et al., Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance, Trends in Immunology (2023). https://doi.org/10.1016/j.it.2023.03.007