What are Thyroid Peroxidase (TPO) antibodies?

From the Guidelines

Thyroid peroxidase antibodies are immune proteins that mistakenly attack the thyroid peroxidase enzyme, leading to autoimmune thyroid diseases, and their presence is a primary marker for Hashimoto's thyroiditis and other thyroid conditions. These antibodies are a key indicator of the immune system's attack on the thyroid gland, potentially causing inflammation and gradual destruction of thyroid tissue, as seen in patients with type 1 diabetes, where autoimmune thyroid disease is the most common autoimmune disorder associated with diabetes, occurring in 17–30% of patients 1. When considering the diagnosis and management of thyroid conditions, it is essential to test for thyroid peroxidase antibodies, especially in individuals with type 1 diabetes, as their presence can be predictive of thyroid dysfunction, most commonly hypothyroidism, although hyperthyroidism can also occur 1. Some key points to consider about thyroid peroxidase antibodies include:

• They can be detected through a simple blood test, with levels above a certain threshold typically considered positive, though reference ranges may vary between laboratories
• Their presence can be detected years before thyroid function changes occur, making them valuable for early diagnosis
• They are particularly important to measure in certain populations, such as individuals with type 1 diabetes, as their presence increases the risk of thyroid dysfunction and may affect glycemic control 1
• While no specific treatment targets the antibodies themselves, their detection helps guide thyroid hormone replacement therapy decisions and monitoring frequency for patients with autoimmune thyroid conditions. In clinical practice, testing for thyroid peroxidase antibodies is recommended soon after the diagnosis of type 1 diabetes, and thyroid-stimulating hormone concentrations should be measured at diagnosis when clinically stable or soon after glycemic control has been established 1.

From the Research

Definition and Function of Thyroid Peroxidase (TPO) Antibodies

• Thyroid peroxidase (TPO) is a key enzyme involved in thyroid hormone synthesis 2.
• Autoantibodies to TPO (TPOAbs) are a hallmark of autoimmune thyroid disease (AITD) 2, 3.
• TPOAbs are directed predominantly to two immunodominant determinants (IDR) termed IDR-A and IDR-B regions, with the latter antibodies more predominant in autoimmune disease 2.

Clinical Significance of TPO Antibodies

• TPOAbs serve as clinical markers of thyroid autoimmune diseases (TAIDs) 4.
• The presence of TPOAbs can be used to diagnose and differentiate between various thyroid disorders, such as Hashimoto's thyroiditis and Graves' disease 3, 4.
• The levels of TPOAbs can vary among patients with different TAIDs, and epitope specificity of antibodies to TPO can help clarify the pathophysiology of these diseases 4.

Epitope Specificity and Binding Constants of TPO Antibodies

• The autoantibodies in blood serum of Hashimoto's thyroiditis patients inhibit the binding of certain monoclonal antibodies (MAbs) to TPO more significantly than those in serum of Graves' disease patients 4.
• Mapping the epitopes to TPO with the help of MAbs may improve the differential diagnosis between different thyroid autoimmunities 4.
• The human anti-TPO autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases shows major features, including the use of specific immunoglobulin variable (V) genes and somatic hypermutations 5.

Structural Studies of TPO and Autoantibodies

• Structural studies of TPO show that the monomer interacts with autoantibodies in thyroid autoimmune disease 6.
• The TPO monomer can exist as a separate entity and bind to patient-derived autoantibodies, revealing conformational changes that bring together previously disparate residues into a continuous epitope 6.