Human papillomavirus, particularly type 18, may be involved in the pathogenesis of thyroid eye disease.
In a new study, researchers at the Bascom Palmer Eye Institute and the University of Miami investigated the possibility of viral molecular mimicry triggering autoimmune responses that contribute to thyroid eye disease (TED).
Their primary objective was to explore whether viral proteins share sequence homologies with human proteins that are implicated in TED, specifically the thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R). Using the Basic Local Alignment Search Tool, the research team identified conserved motifs between viral and human proteins.
Orbital adipose tissue samples were collected from 22 participants—11 patients with TED (seven with chronic disease; four with acute active disease) and 11 controls who underwent blepharoplasty. All samples were tested for antibodies against human papillomavirus type 18 (HPV18) L1 capsid protein using enzyme-linked immunosorbent assays. Statistical analysis included one-way ANOVA, t-tests, and Pearson correlations.
The researchers identified homologous regions—FGXV and IXEXT+NP—between HPV L1 capsid proteins and both the IGF-1R and TSHR. These motifs were conserved across all HPV serotypes, which suggested potential for immune cross-reactivity.
Mean normalized optical density (OD) was 0.94 in controls compared with 2.31 in patients with chronic TED (mean differential [MD] = −1.37, 95% confidence interval [CI] = −2.64 to −0.09, P = .03). OD was significantly higher in acute TED (MD= −3.15, 95% CI = −4.69 to −1.61, P < .001). Patients with acute TED also had higher titers compared with those with chronic TED (MD = −1.78, 95% CI = −3.44 to −0.13, P = .03).
No statistically significant correlations were found between HPV18 immunoglobulin G levels and thyroid function markers, including TSH, free T4, or thyroid-stimulating immunoglobulin. However, elevated titers were observed in patients with TED regardless of teprotumumab treatment status. Differences between patients with untreated TED and controls were significant (MD = −3.22, 95% CI = −5.22 to −1.22, P = .002), as were those between posttreatment patients and controls (MD = −2.89, 95% CI = −5.02 to −0.78, P = .007).
The researchers described the current examination into molecular mimicry, specifically in autoimmune conditions that could heighten HPV, and discussed the quadrivalent HPV vaccine, which “uses virus-like particles from the L1 capsid protein to mimic HPV,” wrote lead study author Ishita Garg, BS, of the Dr. Nasser Ibrahim Al-Rashid Orbital Vision Research Center at the University of Miami Miller School of Medicine, and colleagues. “This study’s findings reveal a homology between L1 capsid and TED’s key targets (IGF-1R and TSHR), suggesting potential autoimmune triggers from HPV exposure or vaccination. Nonetheless, extensive reviews, including a meta-analysis of over 169,000 cases, show no increased autoimmune risk postvaccination, affirming the vaccine’s safety and unlikely role in initiating autoimmune diseases,” they added.
They further explained that HPV vaccination could modulate immune responses that mitigate TED pathogenesis. “[T]he immunologic parallels observed invite a promising avenue for future research in prevention and therapies,” the study authors wrote.
The researchers acknowledged that the small sample size (n = 22) limited generalizability, and the lack of comprehensive HPV infection or vaccination history among the participants constrained causal interpretations.
A full list of disclosures can be found in the published study.
Source: JAMA Ophthalmology