Background. Immunotherapies and targeted therapies are frequently associated with thyroid dysfunction, which is in contrast with the rare thyroid abnormalities induced by cytotoxic agents. Immunotherapy with NY-ESO-1, a tumor-associated antigen expressed by a number of malignancies, was reported to trigger hyperthyroidism or hypothyroidism in two HLA-A2 patients with ovarian cancer. We describe now a case of Graves' disease triggered by NY-ESO-1 in a HLA-A2 negative woman. Patient Findings. A 32-year old woman with a synovial sarcoma, received radiotherapy, chemotherapy, and finally NY-ESO-1 vaccine. The patient typed HLA A11/A33(19), B13/B56(22), Cw3/-. One month after the beginning of immunotherapy, thyroid dysfunction was clinically suspected and Graves' disease was biochemically confirmed. Fearful of the antithyroid drugs' side effects, the patient was treated with a beta-blocker (propranolol, 80 to 20 mg/d). As hyperthyroidism progressively worsened, the patient underwent total thyroidectomy. We hypothesized that NY-ESO-1 shared partial homology with thyroid autoantigens (so-called molecular mimicry mechanism) and that at least one pair of homologous sequences contained amino acid sequence binding motif(s) to a restricted number of HLA molecules. We used the software BLAST to search amino acid sequence homologies between NY-ESO-1 and thyroid autoantigens [TSH-receptor (TSH-R), thyroperoxidase (TPO) and thyroglobulin (Tg)], and the HLA ligand/motif database to look for HLA/T-cell receptor binding motifs in the regions of NY-ESO-1 and thyroid autoantigens that were homologous. We found 15 epitopic regions of NY-ESO-1 homologous to 15 regions of thyroid autoantigens, some of which epitopic: 5 of TSH-R, 8 of Tg, 2 of TPO. These homologous sequences contain binding motifs belonging to several HLA class I antigens, including HLA A2 and the patient's A11 and A33. Summary. Genetically predisposed patients are at risk to develop thyroid dysfunction after vaccine immunotherapy for malignancies.

AUTOIMMUNE THYROID DISEASE ELICITED BY NY-ESO-1 VACCINATION.

VITA, roberto;GUARNERI, Fabrizio Nicola Giuseppe;BENVENGA, Salvatore
2014

Abstract

Background. Immunotherapies and targeted therapies are frequently associated with thyroid dysfunction, which is in contrast with the rare thyroid abnormalities induced by cytotoxic agents. Immunotherapy with NY-ESO-1, a tumor-associated antigen expressed by a number of malignancies, was reported to trigger hyperthyroidism or hypothyroidism in two HLA-A2 patients with ovarian cancer. We describe now a case of Graves' disease triggered by NY-ESO-1 in a HLA-A2 negative woman. Patient Findings. A 32-year old woman with a synovial sarcoma, received radiotherapy, chemotherapy, and finally NY-ESO-1 vaccine. The patient typed HLA A11/A33(19), B13/B56(22), Cw3/-. One month after the beginning of immunotherapy, thyroid dysfunction was clinically suspected and Graves' disease was biochemically confirmed. Fearful of the antithyroid drugs' side effects, the patient was treated with a beta-blocker (propranolol, 80 to 20 mg/d). As hyperthyroidism progressively worsened, the patient underwent total thyroidectomy. We hypothesized that NY-ESO-1 shared partial homology with thyroid autoantigens (so-called molecular mimicry mechanism) and that at least one pair of homologous sequences contained amino acid sequence binding motif(s) to a restricted number of HLA molecules. We used the software BLAST to search amino acid sequence homologies between NY-ESO-1 and thyroid autoantigens [TSH-receptor (TSH-R), thyroperoxidase (TPO) and thyroglobulin (Tg)], and the HLA ligand/motif database to look for HLA/T-cell receptor binding motifs in the regions of NY-ESO-1 and thyroid autoantigens that were homologous. We found 15 epitopic regions of NY-ESO-1 homologous to 15 regions of thyroid autoantigens, some of which epitopic: 5 of TSH-R, 8 of Tg, 2 of TPO. These homologous sequences contain binding motifs belonging to several HLA class I antigens, including HLA A2 and the patient's A11 and A33. Summary. Genetically predisposed patients are at risk to develop thyroid dysfunction after vaccine immunotherapy for malignancies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/2550827
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