Researchers find link between HPV and thyroid eye disease

University of Miami Miller School of Medicine researchers have identified molecular evidence linking human papillomavirus (HPV) to thyroid eye disease (TED) through molecular mimicry involving HPV capsid proteins and autoimmune targets. Elevated antibody levels against HPV appeared in participants with TED, suggesting a possible immunological connection influencing disease development. TED is marked by complex autoimmune features and unclear triggers.

Managing its varied clinical manifestations remains a challenge. Symptoms include proptosis, diplopia, pain, dryness, and redness. Severe cases can lead to vision loss in 2% to 5% of patients.



Among those with Graves disease, TED affects 25% to 50%, and among those with Hashimoto thyroiditis, 3% to 5%. TED also appears in individuals with euthyroidism and hypothyroidism, suggesting additional mechanisms beyond thyroid dysfunction. Autoantibodies that up-regulate insulin-like growth factor-1 receptor (IGF-1R) and thyroid-stimulating hormone receptor (TSHR) have been primarily implicated.

Yet TED cases without thyroid dysfunction prompted hypotheses involving molecular mimicry by pathogens. Reports of TED following coronavirus disease 2019 (COVID-19) infection reinforced this theory and suggested that an infectious agent could trigger autoimmune responses. In the study titled "Human Papillomavirus and Thyroid Eye Disease," published in JAMA Ophthalmology , researchers conducted an experimental study to explore the potential involvement of viral infections in TED pathogenesis.

Orbital adipose tissue samples were collected from 11 patients with TED undergoing orbital decompression surgery and 11 control patients undergoing blepharoplasty. Among the 22 patients, the mean age was 58.6 years, ranging from 37.

4 to 74.4 years. Female patients accounted for 86.

4% of the study population. Researchers used the publicly available Basic Local Alignment Search Tool (BLAST) provided by the National Center for Biotechnology Information (NCBI) to perform protein homology analysis comparing IGF-1R and TSHR against various viral proteomes. Enzyme-linked immunosorbent assays (ELISAs) measured human papillomavirus type 18 (HPV18) L1 immunoglobulin G (IgG) levels from the collected adipose tissue samples.

Optical density (OD) readings from ELISA measured HPV18 L1 IgG antibody levels. OD values were used to estimate the extent of antibody binding detected. Analysis revealed that IGF-1R and TSHR shared homologous sequences with major capsid proteins of the Papillomaviridae family, as well as proteins from Paramyxoviridae, Herpesviridae, Enteroviruses, Polyomaviridae, and Rhabdoviridae families.

Two conserved motifs, FGXV and IXEXT+NP, were identified across all HPV serotypes and both human IGF-1R and TSHR sequences. Mean normalized OD levels for HPV18 L1 IgG differed between groups. Controls had a mean OD of 0.

94. Patients with chronic TED had a mean OD of approximately 2.31, and patients with acute active TED had a mean OD of approximately 4.

09. Both chronic and acute active TED groups showed higher normalized OD levels compared with controls, with acute active TED displaying the highest levels. No correlations appeared between HPV18 L1 IgG levels and thyroid-stimulating hormone, free thyroxine, or thyroid-stimulating immunoglobulin levels.

Radioactive iodine treatment or thyroidectomy did not affect antibody levels. Elevated IgG titers appeared irrespective of treatment with teprotumumab. Researchers concluded that viral molecular mimicry between HPV and key autoimmunity targets, IGF-1R and TSHR, could contribute to the development of TED.

Elevated antibodies against HPV18 L1 capsid protein in patients with TED suggest a potential immunological mechanism influencing disease pathogenesis. Identification of viral mimicry as a possible factor offers new possibilities for prevention strategies and therapeutic approaches. Although the study cohort is small and does not establish causation, recognizing viral exposure as a contributing factor could guide future diagnostic and treatment research.

More information: Ishita Garg et al, Human Papillomavirus and Thyroid Eye Disease, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.

2025.0847 © 2025 Science X Network.