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DOI: 10.1055/s-0034-1372097
Epitope specific immunity in Hashimoto's thyroiditis and papillary thyroid carcinoma: is there a correlation?
Context: Hashimoto's thyroiditis (HT) is a common autoimmune disease leading to thyroid destruction due to lymphocytic infiltration. Papillary thyroid carcinoma (PTC) on the other hand is the most common endocrine tumor. A bidirectional association of HT and PTC is described for a considerable time: (1) histological analyses of HT biopsies often show small PTCs; (2) PTC patients have a higher risk to develop autoimmune thyroiditis. As both disorders show lymphocytic infiltration as well as auto-antibodies directed against thyroglobulin (Tg) and thyroid peroxidase (TPO), the question raises whether there is an immune cross-reactivity in these diseases.
Methods: Six different human leukocyte antigen (HLA)-A2 restricted TPO- or Tg-specific tetramers were synthesized and used for measuring peripheral CD8-positive T cells in PTC patients (n = 36) and healthy controls (n = 17).
Results: The frequency of peripheral TPO- and Tg-specific CD8-positive T cells is significantly higher in HLA-A2-positive PTC patients (0.16 ± 0.1%; 0.17 ± 0.13) in comparison to HLA-A2 negative patients (0.08 ± 0.04, p < 0.05; 0.07 ± 0.05, p < 0.01) and HLA-A2-positive healthy controls (0.04 ± 0.03, p < 0.001; 0.04 ± 0.04, p < 0.001). Subgroup analyses revealed no differences of the number of epitope-specific CD8-positive T cells in tumor burden patients compared to tumor free patients. Correlation analyses between serum anti-Tg levels and the frequency of epitope-specific CD8-positive T cells is currently under consideration as well as functional analyses of epitope-specific cells (in vitro and in vivo).
Conclusion: We here report that both thyroidal antigens, TPO and Tg, are recognized by CD8-positive T cells in PTC patients. We already described exactly these molecules as antigens for HT leading to the characteristic thyroid destruction process. Therefore, our data gives a further hint of how HT and PTC correlate: there seems to be a thyroid specific, cellular cytotoxic immune cross reactivity.