{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:31:56Z","timestamp":1782145916405,"version":"3.54.5"},"posted":{"date-parts":[[2024,4,30]]},"group-title":"Ophthalmology","reference-count":26,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Thyroid eye disease (TED) is an autoimmune disease characterized by orbital inflammation and tissue remodeling. TED pathogenesis is poorly understood but is linked to autoantibodies to thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To explore the potential involvement of viral infections in TED pathogenesis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Using NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, including\n                    <jats:italic>Papillomaviridae<\/jats:italic>\n                    ,\n                    <jats:italic>Paramyxoviridae<\/jats:italic>\n                    ,\n                    <jats:italic>Herpesviridae<\/jats:italic>\n                    ,\n                    <jats:italic>Enterovirus<\/jats:italic>\n                    ,\n                    <jats:italic>Polyomaviridae<\/jats:italic>\n                    , and\n                    <jats:italic>Rhabdoviridae<\/jats:italic>\n                    . Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 22 TED patients and controls to quantify antiviral antibody titers. Demographics and clinical data were reviewed.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Homology analysis revealed conserved motifs between TSHR and IGF-1R with several viral proteins, particularly the human papillomavirus 18 (HPV18) L1 capsid protein. Basic demographic and clinical information between the cohorts were comparable. ELISAs showed statistically significant differences in the average HPV18 L1 IgG normalized optical density levels among tissues of control (\n                    <jats:italic>M<\/jats:italic>\n                    = 0.9387,\n                    <jats:italic>SD<\/jats:italic>\n                    = 0.3548), chronic TED (\n                    <jats:italic>M<\/jats:italic>\n                    = 2.305,\n                    <jats:italic>SD<\/jats:italic>\n                    = 1.064), and active acute TED (\n                    <jats:italic>M<\/jats:italic>\n                    = 4.087,\n                    <jats:italic>SD<\/jats:italic>\n                    = 2.034) patients. These elevated HPV18 L1 IgG titers did not statistically correlate with TSH, T4, or TSI levels, and were elevated in TED patients irrespective of treatment with teprotumumab, indicating a direct immunological response to HPV.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study presents the first molecular evidence linking HPV and TED, highlighting molecular mimicry between HPV capsid protein and key autoimmunity targets in TED. This suggests an immunological link contributing to TED\u2019s pathogenesis, opening new avenues for understanding and managing the disease.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.04.27.24306443","type":"posted-content","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T15:47:06Z","timestamp":1714492026000},"source":"Crossref","is-referenced-by-count":1,"title":["A Novel Association Between Human Papillomavirus and Thyroid Eye Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-7160","authenticated-orcid":false,"given":"Ishita","family":"Garg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin I.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Wester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-5160","authenticated-orcid":false,"given":"Daniel","family":"Pelaez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"8","key":"2024050308200558000_2024.04.27.24306443v1.1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1038\/s41433-021-01593-z","article-title":"Teprotumumab for the treatment of chronic thyroid eye disease","volume":"36","year":"2022","journal-title":"Eye (Lond)"},{"issue":"2","key":"2024050308200558000_2024.04.27.24306443v1.2","first-page":"287","article-title":"2022 Update on Clinical Management of Graves Disease and Thyroid Eye Disease","volume":"51","year":"2022","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"1","key":"2024050308200558000_2024.04.27.24306443v1.3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40123-019-00226-9","article-title":"Current Understanding of the Progression and Management of Thyroid Associated Orbitopathy: A SystemaEc Review","volume":"9","year":"2020","journal-title":"Ophthalmol Ther"},{"key":"2024050308200558000_2024.04.27.24306443v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0806317"},{"issue":"1","key":"2024050308200558000_2024.04.27.24306443v1.5","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13023-017-0625-1","article-title":"Graves\u2019 orbitopathy as a rare disease in Europe: a European Group on Graves\u2019 Orbitopathy (EUGOGO) posiEon statement","volume":"12","year":"2017","journal-title":"Orphanet J Rare Dis"},{"key":"2024050308200558000_2024.04.27.24306443v1.6","first-page":"543","article-title":"Update on thyroid eye disease and management","volume":"3","year":"2009","journal-title":"Clin Ophthalmol"},{"key":"2024050308200558000_2024.04.27.24306443v1.7","doi-asserted-by":"crossref","unstructured":"Fernando, R. , O. 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