Recent advances in understanding autoimmune thyroid disease: the tallest tree in the forest of polyautoimmunity

Abstract

Autoimmune thyroid disease (AITD) is often observed together with other autoimmune diseases. The coexistence of two or more autoimmune diseases in the same patient is referred to as polyautoimmunity, and AITD is the autoimmune disease most frequently involved. The occurrence of polyautoimmunity has led to the hypothesis that the affected patients suffer from a generalized dysregulation of their immune system. The present review summarizes recent discoveries unravelling the immunological mechanisms involved in autoimmunity, ranging from natural autoimmunity to disease-specific autoimmunity. Furthermore, the clinical grounds for considering AITD in a setting of polyautoimmunity are explored. A better understanding of these may pave the way for designing new treatment modalities targeting the underlying immune dysregulation when AITD appears in the context of polyautoimmunity.

Keywords: AITD; Graves' disease; Hashimoto's thyroiditis; Thyroid autoimmunity; antibodies; autoimmune disease; immunology; polyautoimmunity.

Figure 1.. B-cell and T-cell subsets controlling autoimmunity.

Peripheral self-tolerance is ensured by regulatory B cells and T cells. Autoimmunity (loss of self-tolerance) is considered to be due to a shift in favor of pro-inflammatory effector cells. B _eff, effector B cells; B _reg, regulatory B cells; DC, dendritic cell; IL, interleukin; iT _reg, induced regulatory T cells; TGF-β, transforming growth factor beta; Th _1,2,17, effector CD4 ⁺ T-cell subsets with different cytokine profiles.

Figure 2.. Etiology of thyroid autoimmunity.

The development of autoimmune thyroid disease is a result of multiple events—a “Swiss cheese model”. Figure reproduced with kind permission from Weetman . HLA, human leukocyte antigen.