Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance

[helvella]

A very recent paper which looks at the connections between autoimmune thyroid diseases. Surely many here have had questions over the years. Especially those who switched between the forms.

Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance

Tomer Milo

Yael Korem Kohanim

Yoel Toledano

Uri Alon

Open Access Published: April 13, 2023

DOI: doi.org/10.1016/j.it.2023.0...

Highlights

Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are common human thyroid autoimmune diseases with opposite clinical manifestations.

GD and HT originate from T cells that are autoreactive to thyroid-stimulating hormone (TSH) receptor antigens and to thyroglobulin (Tg)/thyroid peroxidase (TPO) antigens, respectively.

The two diseases exhibit shared risk factors and incidence curves, and can interconvert.

The autoimmune surveillance theory provides a rationale for a putative shared etiology between the two diseases based on a physiological circuit of a mutant removal mechanism.

Autoreactive T cells are suggested to weed out hypersecreting mutants in the thyroid, with the cost of triggering a humoral response, leading to GD or HT in susceptible individuals.

Significance

The origin of the two autoimmune diseases of the thyroid (Graves’ disease and Hashimoto's thyroiditis) remains insufficiently understood. Despite their opposite clinical manifestations of hyper- and hypothyroidism, we propose a shared origin based on a physiological autoimmune surveillance mechanism against hypersecreting mutant cells, which may explain observed links between these diseases.

Abstract

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.

Keywords

physiological autoimmunity

Graves' disease

Hashimoto's thyroiditis

thyroid autoimmune diseases

autoimmune etiology

systems immunology

cell.com/trends/immunology/...

Note the thanks to Johannes Dietrich!

[arTistapple]

Frankly it seems good to me that someone is looking at this. Quite a different creativity than that of the dull institutionalised thinking we are subjected to by the NHS.

[helvella Administrator Thyroid UK in reply to arTistapple]

Even if they are completely wrong, it is necessary to have investigated and considered the possibility.

[TSH110 in reply to helvella]

it has often been postulated they are heads of the same beast even in old papers. Good that someone is looking for a mechanism to explain it. I suspect they are from the same origin.

[helvella Administrator Thyroid UK in reply to TSH110]

Indeed.

Alongside "official" information which absolutely insists that Graves opthalmopathy/Thyroid Eye Disease/'whatever it is called today' ONLY occurs in hyperthyroidism and specifically Graves disease.

As so often, casting adrift anyone who has GO without Graves Disease and condemning them to very serious consequences.

[tattybogle]

I've had the opinion that they are "the same basic problem manifested in different ways in different bodies" ever since i realised the % of people with 'one' who have antibodies for the 'other' .. and presumably those %'s we have are gross underestimate , since we know how little data they gather about TRab antibodies in 'hypothyroid' patients.

thyroidpatients.ca/2020/04/...

https://thyroidpatients.ca/2020/04/12/the-spectrum-of-thyroid-autoimmunity/

[TSH110 in reply to tattybogle]

it’s a great blog article from the splendid - Tania it really opened my eyes big time to what these disorders actually are not lone entities but part of a group with subtle differences in antibody involvement