The Cross-Knit Between Immune Cells and Thyroid Function in Autoimmune Thyroid Disorders: What We Can Learn from Inborn Errors of Immunity

TL;DR

This paper explores how immune system defects in rare genetic disorders can help us understand the causes of autoimmune thyroid diseases.

Contribution

The paper proposes that inborn errors of immunity serve as a model to study immune tolerance breakdown in autoimmune thyroid diseases.

Findings

Autoimmune thyroid diseases share pathogenetic mechanisms with inborn errors of immunity.

Genetic and epigenetic changes in immune tolerance contribute to thyroid autoimmunity.

Immune defects in rare disorders can reveal molecular pathways driving autoimmune thyroid diseases.

Abstract

What are the main findings?
Autoimmune thyroid diseases (AITDs) share key pathogenetic mechanisms with inborn errors of immunity (IEIs), making IEIs a natural model to study immune tolerance breakdown.Genetic and epigenetic perturbations affecting central and peripheral tolerance mechanisms contribute to the development of thyroid autoimmunity.

Autoimmune thyroid diseases (AITDs) share key pathogenetic mechanisms with inborn errors of immunity (IEIs), making IEIs a natural model to study immune tolerance breakdown.

Genetic and epigenetic perturbations affecting central and peripheral tolerance mechanisms contribute to the development of thyroid autoimmunity.

What is the implication of the main findings?
Understanding how specific immune defects lead to AITDs enables the identification of precise molecular pathways driving thyroid autoimmunity.These insights support the development of targeted, pathway-specific therapies and precision-medicine approaches for AITDs.

Understanding how specific immune defects lead to AITDs enables the identification of precise molecular pathways driving thyroid autoimmunity.

These insights support the development of targeted, pathway-specific therapies and precision-medicine approaches for AITDs.

Autoimmune thyroid diseases (AITDs), including Hashimoto thyroiditis and Graves’ disease, are the most common autoimmune endocrinopathies, affecting up to 5% of the population. Pathogenetic pathways have not yet been fully elucidated, even though different immune-genetic alterations have been proposed. Specific immune defects presenting with AITDs may serve as an experimentum naturae to study the involvement of a specific pathway in the pathogenesis of the disease. In fact, since immune dysregulation with autoimmunity frequently characterize inborn errors of immunity (IEIs), understanding the mechanisms of immune tolerance breakdown leading to autoimmunity in these conditions may provide useful insight to understand the pathogenesis of AITDs. In this review, we will highlight the main immunological aspects of AITDs and their pathogenesis in IEIs.

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