Human Papillomavirus and Thyroid Eye Disease

Importance 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 insulinlike growth factor-1 receptor (IGF-1R). Objective To explore the potential involvement of viral infections in TED pathogenesis. Design, Setting, and Participants In this experimental study conducted at the Bascom Palmer Eye Institute in Miami, Florida, the National Center for Biotechnology Information Basic Local Alignment Search Tool was used to search for amino acid sequence homologies between TSHR and IGF-1R proteins to various viral proteomes, including Papillomaviridae , Paramyxoviridae , Herpesviridae , Enterovirus , Polyomaviridae , and Rhabdoviridae . Participants were enrolled from December 2021 to August 2023, with the samples tested and analyzed in September 2023. Enzyme-linked immunoassays (ELISAs) were performed on orbital adipose tissue samples from 11 participants with TED undergoing orbital decompression surgery and 11 control participants undergoing blepharoplasty to quantify antiviral antibody titers. Demographic characteristics and clinical data were reviewed. Main Outcomes and Measures The main outcomes were homology analysis between TSHR and IGF-1R with several viral proteins, human papillomavirus 18 (HPV18) L1 immunoglobulin G (IgG) titers in TED orbital fat samples, and clinical characteristics associated with HPV18 L1 IgG titers. Results Among 22 total patients, mean (range) age was 58.6 years (37.4-74.4), and 19 patients (86.4%) were female. Homology analysis revealed conserved motifs between TSHR and IGF-1R with the HPV18 L1 capsid protein. Homologous regions of FG X V and I X E X T+NP were identified across all HPV serotypes and both IGF-1R and TSHR. ELISAs showed differences in the mean HPV18 L1 IgG normalized optical density levels among tissues of controls vs participants with chronic TED (mean [ M ], 0.94; mean differential, −1.37; 95% CI, −2.64 to −0.09; P = .03), controls vs participants with acute active TED ( M , 0.94; mean differential, −3.15; 95% CI, −4.69 to −1.61; P < .001), and participants with chronic TED vs acute active TED ( M , 2.31; mean differential, −1.78; 95% CI, −3.44 to −0.13; P = .03). Conclusions and Relevance This case-control study presents potential 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’s pathogenesis, opening new potential avenues for understanding and management of the disease.