{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:54:22Z","timestamp":1790873662478,"version":"4.1.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Immune checkpoint inhibitors (ICIs) frequently cause thyroid dysfunction but their underlying mechanism remains unclear. We have previously demonstrated increased circulating natural killer (NK) cells and human leukocyte antigen (HLA)-DR surface expression on inflammatory intermediate CD14\n                      <jats:sup>+<\/jats:sup>\n                      CD16\n                      <jats:sup>+<\/jats:sup>\n                      monocytes in programmed cell death protein-1 (PD-1) inhibitor-treated patients. This study characterizes intrathyroidal and circulating immune cells and class II HLA in ICI-induced thyroiditis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      This is a single-center prospective cohort study of 10 patients with ICI-induced thyroiditis by flow cytometry of thyroid fine needle aspirates (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20099) and peripheral blood (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20097) as compared with healthy thyroid samples (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095) and healthy volunteer blood samples (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200944); HLA class II was tested in\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20099.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      ICI-induced thyroiditis samples demonstrated overall increased T lymphocytes (61.3% vs. 20.1%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.00006), CD4\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>\u2212<\/jats:sup>\n                      T lymphocytes (1.9% vs. 0.7%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.006), and, as a percent of T lymphocytes, increased CD8\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes (38.6% vs. 25.7%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0259) as compared with healthy thyroid samples. PD-1 inhibitor-induced thyroiditis had increased CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD1\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes (40.4% vs. 0.8%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.021) and CD8\n                      <jats:sup>+<\/jats:sup>\n                      PD1\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes (28.8% vs. 1.5%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.038) in the thyroid compared with the blood. Circulating NK cells, certain T lymphocytes (CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      , CD4\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>\u2212<\/jats:sup>\n                      T, gamma\n                      <jats:bold>\u2013<\/jats:bold>\n                      delta), and intermediate monocytes were increased in ICI-induced thyroiditis. Six patients typed as HLA-DR4-DR53 and three as HLA-DR15.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      ICI-induced thyroiditis is a T lymphocyte-mediated process with intra-thyroidal predominance of CD8\n                      <jats:sup>+<\/jats:sup>\n                      and CD4\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD8\n                      <jats:sup>\u2212<\/jats:sup>\n                      T lymphocytes. The HLA haplotypes may be involved but need further evaluation. These findings expand the limited understanding of ICI-induced thyroiditis, which could be further translated to guide immunomodulatory therapies for advanced thyroid cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0075","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T05:53:12Z","timestamp":1587621192000},"page":"1440-1450","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":89,"title":["Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations"],"prefix":"10.1177","volume":"30","author":[{"given":"Anupam","family":"Kotwal","sequence":"first","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA."},{"name":"Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA."},{"name":"Division of Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Bornschlegl","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Kottschade","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danae A.","family":"Delivanis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan B.","family":"Dietz","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabel","family":"Ryder","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA."},{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00448"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0562"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0499"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw640"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4075"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000293"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2300"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0116"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00432"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000464285"},{"key":"e_1_3_6_12_2","first-page":"2087525","article-title":"Treatment of ipilimumab induced Graves' disease in a patient with metastatic melanoma","volume":"2016","author":"Azmat U","year":"2016","unstructured":"Azmat U, , Liebner D, , Joehlin-Price A, , Agrawal A, , Nabhan F. 2016. 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