Garg Ishita, Meyer Benjamin I, Gallo Ryan A, Wester Sara T, Pelaez Daniel
Dr Nasser Ibrahim Al-Rashid Orbital Vision Research Center, McKnight Vision Research Center, University of Miami Miller School of Medicine, Miami, Florida.
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida.
JAMA Ophthalmol. 2025 Apr 24. doi: 10.1001/jamaophthalmol.2025.0847.
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).
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.
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.
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 FGXV and IXEXT+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).
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.
甲状腺眼病（TED）是一种自身免疫性疾病，其特征为眼眶炎症和组织重塑。TED的发病机制尚不清楚，但与促甲状腺激素受体（TSHR）和胰岛素样生长因子-1受体（IGF-1R）的自身抗体有关。
探讨病毒感染在TED发病机制中的潜在作用。
设计、地点和参与者：在佛罗里达州迈阿密的巴斯科姆·帕尔默眼科研究所进行的这项实验研究中，使用美国国立生物技术信息中心基本局部比对搜索工具，搜索TSHR和IGF-1R蛋白与各种病毒蛋白质组（包括乳头瘤病毒科、副粘病毒科、疱疹病毒科、肠道病毒、多瘤病毒科和弹状病毒科）之间的氨基酸序列同源性。参与者于2021年12月至2023年8月入组，样本于2023年9月进行检测和分析。对11例接受眼眶减压手术的TED患者和11例接受眼睑成形术的对照参与者的眼眶脂肪组织样本进行酶联免疫吸附测定（ELISA），以量化抗病毒抗体滴度。回顾了人口统计学特征和临床数据。
主要结局为TSHR和IGF-1R与几种病毒蛋白的同源性分析、TED眼眶脂肪样本中人乳头瘤病毒18（HPV18）L1免疫球蛋白G（IgG）滴度，以及与HPV18 L1 IgG滴度相关的临床特征。
在22例患者中，平均（范围）年龄为58.6岁（37.4 - 74.4岁），19例患者（86.4%）为女性。同源性分析显示TSHR和IGF-1R与HPV18 L1衣壳蛋白之间存在保守基序。在所有HPV血清型以及IGF-1R和TSHR中均鉴定出FGXV和IXEXT + NP的同源区域。ELISA显示，对照组织与慢性TED参与者组织之间的平均HPV18 L1 IgG标准化光密度水平存在差异（平均值[M]，0.94；平均差异，-1.37；95%置信区间，-2.64至-0.09；P = 0.03），对照组织与急性活动性TED参与者组织之间存在差异（M，0.94；平均差异，-3.15；95%置信区间，-4.69至-1.61；P < 0.001），慢性TED参与者与急性活动性TED参与者之间存在差异（M，2.31；平均差异，-1.78；95%置信区间，-3.44至-0.13；P = 0.03）。
这项病例对照研究提供了将HPV与TED联系起来的潜在分子证据，突出了HPV衣壳蛋白与TED关键自身免疫靶点之间的分子模拟。这表明存在一种免疫联系，有助于TED的发病机制，为该疾病的理解和管理开辟了新的潜在途径。
