Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients' T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?
The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves' disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). Twenty subjects matched for age and sex without known thyroid disease served as controls. In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter. Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain. Six to 8 weeks after subtotal thyroidectomy, the number of patients' PBMC responding to any peptide and the average number of recognized peptides decreased. A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery. The responses of PBMC from Graves' patients before RAI therapy were less than those in the presurgical group. Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased. Three to 6 months after RAI, T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy, but still higher than the values on day 0. Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy. The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment. TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy. The difference in the number of recognized peptides by patients' PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery. The decreased T cell reactivity to thyroid antigens after thyroidectomy could be the result of removal of a major part of the thyroid gland or redistribution of suppressor-inducer T cells. The increased T cell response after RAI therapy is probably epitope specific, rather than a response to the whole TSHR molecule. Synchronous recognition of peptides 158-176 and 248-263 is important for the development of GD, and the loss of recognition of one of these epitopes may be an early sign of immune remission and a predictor of euthyroidism.
Soliman
M
M
Department of Medicine, University of Chicago, Illinois 60637, USA.
Kaplan
E
E
Abdel-Latif
A
A
Scherberg
N
N
DeGroot
L J
LJ
D000328:Adult; D000911:Antibodies, Monoclonal; D013956:Antithyroid Agents / Q000627:therapeutic use*; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D011988:Receptors, Thyroid Hormone / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors
D000911:Antibodies, Monoclonal; D013956:Antithyroid Agents; D000939:Epitopes; D007457:Iodine Radioisotopes; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D013972:Thyrotropin; D013954:Thyroglobulin