What is the origin of Thyroid Peroxidase (TPO) antibodies?

Origin of Thyroid Peroxidase (TPO) Antibodies

TPO antibodies originate from B cells as part of an autoimmune response targeting the thyroid peroxidase enzyme, which is present on the apical surface of thyroid follicular cells and serves as the primary antigen involved in cell-mediated cytotoxicity in autoimmune thyroid disease. 1

Cellular and Molecular Origin

TPO antibodies are:

• Produced by thyroid tissue-infiltrating B cells 2
• Primarily of IgG class 2
• Associated with thyroid destruction and hypothyroidism 2
• Directed against the thyroid peroxidase enzyme, which was originally described as the thyroid microsomal antigen 1, 3

Genetic and Immunological Factors

The development of TPO antibodies involves multiple factors:

1. Genetic components:

   • HLA linkage plays a role in susceptibility 1
   • TPO autoantibody V region genes are not unique; H chain V genes are usually mutated 2
   • Some L chain V genes remain in germ-line conformation 2
   • Familial patterns suggest inheritance of epitopic fingerprints 2

2. Epitope recognition:

   • TPO antibodies recognize an immunodominant region involving conformational, overlapping epitopes 2
   • Multiple B-cell-reactive epitopes exist, each giving rise to different antibodies 1
   • Epitopic fingerprints are distinctive for individual sera and are conserved over time 2

3. Environmental triggers:

   • Environmental factors interact with genetic predisposition 1
   • Smoking is associated with higher odds of TPO antibody detectability 4
   • Alcohol consumption is associated with lower odds of TPO antibodies 4

Clinical Significance

TPO antibodies are:

• Present in almost all patients with Hashimoto's thyroiditis 5
• Present in more than 70% of patients with Graves' disease 5
• Found to variable degrees in patients with non-thyroid autoimmune diseases 5
• Present in some normal subjects 5

Important Clinical Correlations

• There is a good correlation between the degree of lymphocytic infiltration of the thyroid gland and the titer of TPO antibodies 5
• Screening for TPO antibodies should be performed in women with premature ovarian insufficiency (POI) of unknown cause or if an immune disorder is suspected 6
• In patients with a positive TPO antibody test, thyroid stimulating hormone (TSH) should be measured every year 6
• Detectable TPO antibodies are associated with higher risk of overall, cancer-related, and cardiovascular mortality, particularly in men 4

Sex Differences and Risk Factors

• Female sex is a significant determinant of TPO antibody positivity (OR = 2.47) 4
• Current smoking is strongly associated with TPO antibody detectability (OR = 3.10) 4
• Higher age is associated with lower odds of TPO antibody detectability 4
• All categories of alcohol consumption are associated with lower odds of TPO antibody detectability 4

Clinical Applications

TPO antibodies serve as:

• A marker for defining autoimmune thyroid diseases 5
• A tool for detecting an underlying autoimmune process in the thyroid 5
• A predictor of risk for developing hypothyroidism during subclinical thyroid disease 1
• A potential marker for low-grade inflammation 4

Monitoring Considerations

• In patients with premature ovarian insufficiency, if TPO antibodies are negative, there is no indication for re-testing later in life, unless signs or symptoms of thyroid disease develop 6
• Patients with positive TPO antibodies who become pregnant should increase levothyroxine dose by approximately 30% and monitor TSH monthly during pregnancy 7

TPO antibodies remain a crucial biomarker in thyroid autoimmunity, providing valuable diagnostic and prognostic information while reflecting the underlying pathophysiology of autoimmune thyroid disorders.