A Novel Association Between Human Papillomavirus and Thyroid Eye Disease

Abstract

ABSTRACTContextThyroid 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).ObjectiveTo explore the potential involvement of viral infections in TED pathogenesis.MethodsUsing NCBI BLAST, we compared human TSHR and IGF-1R proteins to various viral proteomes, includingPapillomaviridae,Paramyxoviridae,Herpesviridae,Enterovirus,Polyomaviridae, andRhabdoviridae. 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.ResultsHomology 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 (M= 0.9387,SD= 0.3548), chronic TED (M= 2.305,SD= 1.064), and active acute TED (M= 4.087,SD= 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.ConclusionsThis 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’s pathogenesis, opening new avenues for understanding and managing the disease.