{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:54:50Z","timestamp":1794005690847,"version":"4.8.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["EY08976"],"award-info":[{"award-number":["EY08976"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eye"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1038\/s41433-018-0265-2","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T14:19:47Z","timestamp":1541081987000},"page":"200-205","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The insulin-like growth factor-I receptor and its role in thyroid-associated ophthalmopathy"],"prefix":"10.1038","volume":"33","author":[{"given":"Terry J.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"265_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1210\/edrv-16-2-143","volume":"16","author":"D LeRoith","year":"1995","unstructured":"LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. 1995;16:143\u201363.","journal-title":"Endocr Rev"},{"key":"265_CR2","first-page":"3","volume":"16","author":"JI Jones","year":"1995","unstructured":"Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3\u201334.","journal-title":"Endocr Rev"},{"key":"265_CR3","first-page":"761","volume":"20","author":"V Hwa","year":"1999","unstructured":"Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev. 1999;20:761\u201387.","journal-title":"Endocr Rev"},{"key":"265_CR4","unstructured":"LeRoith DAD, Werner H, Roberts C Jr. Molecular and cellular biology of the insulin-like growth factors. In: Weintraub BD, editor. Molecular endocrinology, basic concepts and clinical correlations. New York, NY: Raven Press; 1995. p. 181\u201393."},{"key":"265_CR5","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1124\/pr.109.002469","volume":"62","author":"TJ Smith","year":"2010","unstructured":"Smith TJ. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol Rev. 2010;62:199\u2013236.","journal-title":"Pharmacol Rev"},{"key":"265_CR6","doi-asserted-by":"crossref","unstructured":"De Meyts PSW, Palsgaard J, Theede A, Gaugain L, Aladdin H, Whittaker J. Insulin and IGF-I receptor structure and binding mechanism. In: Pessin JE, Saltiel AR, editors. Mechanisms of insulin action. Austin, TX: Landes Bioscience; 2007. p. 1\u201332.","DOI":"10.1007\/978-0-387-72204-7_1"},{"key":"265_CR7","doi-asserted-by":"publisher","first-page":"39684","DOI":"10.1074\/jbc.M202766200","volume":"277","author":"G Pandini","year":"2002","unstructured":"Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin\/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277:39684\u201395.","journal-title":"J Biol Chem"},{"key":"265_CR8","doi-asserted-by":"publisher","first-page":"25869","DOI":"10.1074\/jbc.M605189200","volume":"281","author":"R Slaaby","year":"2006","unstructured":"Slaaby R, Schaffer L, Lautrup-Larsen I, Andersen AS, Shaw AC, Mathiasen IS, et al. Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. J Biol Chem. 2006;281:25869\u201374.","journal-title":"J Biol Chem"},{"key":"265_CR9","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.1365-2184.1994.tb01406.x","volume":"27","author":"R Baserga","year":"1994","unstructured":"Baserga R, Sell C, Porcu P, Rubini M. The role of the IGF-I receptor in the growth and transformation of mammalian cells. Cell Prolif. 1994;27:63\u201371.","journal-title":"Cell Prolif"},{"key":"265_CR10","doi-asserted-by":"crossref","first-page":"29501","DOI":"10.18632\/oncotarget.15704","volume":"8","author":"X Qu","year":"2017","unstructured":"Qu X, Wu Z, Dong W, Zhang T, Wang L, Pang Z, et al. Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy. Oncotarget. 2017;8:29501\u201318.","journal-title":"Oncotarget"},{"key":"265_CR11","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1007\/s00018-013-1514-y","volume":"71","author":"L Girnita","year":"2014","unstructured":"Girnita L, Worrall C, Takahashi S, Seregard S, Girnita A. Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation. Cell Mol Life Sci. 2014;71:2403\u201327.","journal-title":"Cell Mol Life Sci"},{"key":"265_CR12","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","volume":"375","author":"TJ Smith","year":"2016","unstructured":"Smith TJ, Hegedus L. Graves\u2019 disease. N Engl J Med. 2016;375:1552\u201365.","journal-title":"N Engl J Med"},{"key":"265_CR13","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1210\/endo-68-1-154","volume":"68","author":"DD Adams","year":"1961","unstructured":"Adams DD, Purves HD, Sirett NE. The response of hypophysectomized mice to injections of human serum containing long-acting thyroid stimulator. Endocrinology. 1961;68:154\u20135.","journal-title":"Endocrinology"},{"key":"265_CR14","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1167\/iovs.14-14002","volume":"55","author":"Y Wang","year":"2014","unstructured":"Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014;55:1735\u201348.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"265_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0478-4","volume":"6","author":"G Masetti","year":"2018","unstructured":"Masetti G, Moshkelgosha S, Kohling HL, Covelli D, Banga JP, Berchner-Pfannschmidt U, et al. Gut microbiota in experimental murine model of Graves\u2019 orbitopathy established in different environments may modulate clinical presentation of disease. Microbiome. 2018;6:97.","journal-title":"Microbiome"},{"key":"265_CR16","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3109\/08916939309014643","volume":"16","author":"DR Weightman","year":"1993","unstructured":"Weightman DR, Perros P, Sherif IH, Kendall-Taylor P. Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy. Autoimmunity. 1993;16:251\u20137.","journal-title":"Autoimmunity"},{"key":"265_CR17","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1210\/jcem-62-2-357","volume":"62","author":"CM Rotella","year":"1986","unstructured":"Rotella CM, Zonefrati R, Toccafondi R, Valente WA, Kohn LD. Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves\u2019 sera. J Clin Endocrinol Metab. 1986;62:357\u201367.","journal-title":"J Clin Endocrinol Metab"},{"key":"265_CR18","first-page":"691","volume":"84","author":"P Perros","year":"1992","unstructured":"Perros P, Kendall-Taylor P. Biological activity of autoantibodies from patients with thyroid-associated ophthalmopathy: in vitro effects on porcine extraocular myoblasts. Q J Med. 1992;84:691\u2013706.","journal-title":"Q J Med"},{"key":"265_CR19","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1210\/endo-119-2-940","volume":"119","author":"D Tramontano","year":"1986","unstructured":"Tramontano D, Cushing GW, Moses AC, Ingbar SH. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves\u2019-IgG. Endocrinology. 1986;119:940\u20132.","journal-title":"Endocrinology"},{"key":"265_CR20","doi-asserted-by":"publisher","first-page":"6348","DOI":"10.4049\/jimmunol.170.12.6348","volume":"170","author":"J Pritchard","year":"2003","unstructured":"Pritchard J, Han R, Horst N, Cruikshank WW, Smith TJ. Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves\u2019 disease is mediated through the insulin-like growth factor I receptor pathway. J Immunol. 2003;170:6348\u201354.","journal-title":"J Immunol"},{"key":"265_CR21","doi-asserted-by":"publisher","first-page":"942","DOI":"10.4049\/jimmunol.168.2.942","volume":"168","author":"J Pritchard","year":"2002","unstructured":"Pritchard J, Horst N, Cruikshank W, Smith TJ. Igs from patients with Graves\u2019 disease induce the expression of T cell chemoattractants in their fibroblasts. J Immunol. 2002;168:942\u201350.","journal-title":"J Immunol"},{"key":"265_CR22","doi-asserted-by":"publisher","first-page":"3281","DOI":"10.4049\/jimmunol.178.5.3281","volume":"178","author":"RS Douglas","year":"2007","unstructured":"Douglas RS, Gianoukakis AG, Kamat S, Smith TJ. Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves\u2019 disease may carry functional consequences for disease pathogenesis. J Immunol. 2007;178:3281\u20137.","journal-title":"J Immunol"},{"key":"265_CR23","doi-asserted-by":"publisher","first-page":"5768","DOI":"10.4049\/jimmunol.181.8.5768","volume":"181","author":"RS Douglas","year":"2008","unstructured":"Douglas RS, Naik V, Hwang CJ, Afifiyan NF, Gianoukakis AG, Sand D, et al. B cells from patients with Graves\u2019 disease aberrantly express the IGF-1 receptor: implications for disease pathogenesis. J Immunol. 2008;181:5768\u201374.","journal-title":"J Immunol"},{"key":"265_CR24","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.4049\/jimmunol.138.11.3817","volume":"138","author":"WW Cruikshank","year":"1987","unstructured":"Cruikshank WW, Berman JS, Theodore AC, Bernardo J, Center DM. Lymphokine activation of T4+ T lymphocytes and monocytes. J Immunol. 1987;138:3817\u201323.","journal-title":"J Immunol"},{"key":"265_CR25","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.4049\/jimmunol.141.3.1018","volume":"141","author":"TJ Schall","year":"1988","unstructured":"Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, et al. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988;141:1018\u201325.","journal-title":"J Immunol"},{"key":"265_CR26","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1210\/jc.2012-1771","volume":"98","author":"WB Minich","year":"2013","unstructured":"Minich WB, Dehina N, Welsink T, Schwiebert C, Morgenthaler NG, Kohrle J, et al. Autoantibodies to the IGF1 receptor in Graves\u2019 orbitopathy. J Clin Endocrinol Metab. 2013;98:752\u201360.","journal-title":"J Clin Endocrinol Metab"},{"key":"265_CR27","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1210\/jc.2014-3566","volume":"100","author":"CC Krieger","year":"2015","unstructured":"Krieger CC, Neumann S, Place RF, Marcus-Samuels B, Gershengorn MC. Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by Graves\u2019 disease immunoglobins. J Clin Endocrinol Metab. 2015;100:1071\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"265_CR28","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1210\/jc.2012-2270","volume":"98","author":"AJ Varewijck","year":"2013","unstructured":"Varewijck AJ, Boelen A, Lamberts SW, Fliers E, Hofland LJ, Wiersinga WM, et al. Circulating IgGs may modulate IGF-I receptor stimulating activity in a subset of patients with Graves\u2019 ophthalmopathy. J Clin Endocrinol Metab. 2013;98:769\u201376.","journal-title":"J Clin Endocrinol Metab"},{"key":"265_CR29","doi-asserted-by":"crossref","unstructured":"Marino M, Rotondo Dottore G, Ionni I, Lanzolla G, Sabini E, Ricci D, et al. Serum antibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves\u2019 disease and Graves\u2019 orbitopathy. J Endocrinol Invest. 2018.","DOI":"10.1007\/s40618-018-0943-8"},{"key":"265_CR30","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1210\/en.2013-1576","volume":"154","author":"S Moshkelgosha","year":"2013","unstructured":"Moshkelgosha S, So PW, Deasy N, Diaz-Cano S, Banga JP. Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of Graves\u2019 orbitopathy induced by thyrotropin receptor plasmid-in vivo electroporation. Endocrinology. 2013;154:3008\u201315.","journal-title":"Endocrinology"},{"key":"265_CR31","doi-asserted-by":"publisher","first-page":"3564","DOI":"10.4049\/jimmunol.173.5.3564","volume":"173","author":"J Pritchard","year":"2004","unstructured":"Pritchard J, Tsui S, Horst N, Cruikshank WW, Smith TJ. Synovial fibroblasts from patients with rheumatoid arthritis, like fibroblasts from Graves\u2019 disease, express high levels of IL-16 when treated with Igs against insulin-like growth factor-1 receptor. J Immunol. 2004;173:3564\u20139.","journal-title":"J Immunol"},{"key":"265_CR32","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.4049\/jimmunol.181.6.4397","volume":"181","author":"S Tsui","year":"2008","unstructured":"Tsui S, Naik V, Hoa N, Hwang CJ, Afifiyan NF, Sinha Hikim A, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves\u2019 disease. J Immunol. 2008;181:4397\u2013405.","journal-title":"J Immunol"},{"key":"265_CR33","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","volume":"376","author":"TJ Smith","year":"2017","unstructured":"Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748\u201361.","journal-title":"N Engl J Med"}],"container-title":["Eye"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41433-018-0265-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-018-0265-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41433-018-0265-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:16:05Z","timestamp":1694020565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41433-018-0265-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["265"],"URL":"https:\/\/doi.org\/10.1038\/s41433-018-0265-2","relation":{},"ISSN":["0950-222X","1476-5454"],"issn-type":[{"value":"0950-222X","type":"print"},{"value":"1476-5454","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,1]]},"assertion":[{"value":"10 October 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The author has been issued patents covering his invention of using IGF-I receptor inhibition as a therapy for Graves\u2019 disease, TAO, and other autoimmune diseases. These are held by the Los Angeles Biomedical Institute and the UCLA School of Medicine.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}