Differentiation between thyroid‐associated orbitopathy and Graves’ disease by iTRAQ‐based quantitative proteomic analysis

Kang, Jianshu; Li, Yunqin; Zhao, Zhong-Qiu; Zhang, Hong

doi:10.1002/2211-5463.13172

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Complement C4A is an inflammation-related protein, and its content varies in different inflammatory diseases, such as GO and GD. Another study has confirmed that complement C4A is markedly upregulated in serum samples of GO patients compared with controls (20).…”

Section: Biomarker Discovery Between the Go Group And Gd Groupmentioning

confidence: 83%

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

et al. 2022

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Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.

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Section: Biomarker Discovery Between the Go Group And Gd Groupmentioning

confidence: 83%

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

et al. 2022

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“…Inflammatory response: ER oxidative stress induces the release of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), which contribute to inflammation, edema, and fibrosis in ocular tissues associated with TAO ( 54 , 55 ). Furthermore, ER oxidative stress disrupts calcium ion homeostasis, crucial for cell signaling and regulation ( 56 ).…”

Section: Oxidative Stress In Taomentioning

confidence: 99%

Thyroid-associated ophthalmopathy: the role of oxidative stress

Ma,

Li,

et al. 2024

Front. Endocrinol.

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Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition affecting the eyes, characterized by proptosis, extraocular muscle involvement, and in severe cases, vision impairment including diplopia, optic neuropathy, and potential blindness. The exact etiology of TAO remains elusive; however, increased oxidative stress and decreased antioxidant capacity are pivotal in its pathogenesis. Elevated oxidative stress not only directly damages orbital tissues but also influences thyroid function and autoimmune responses, exacerbating tissue destruction. This review explores the role of oxidative stress in TAO, elucidates its mechanisms, and evaluates the efficacy and limitations of antioxidant therapies in managing TAO. The findings aim to enhance understanding of oxidative stress mechanisms in TAO and propose potential antioxidant strategies for future therapeutic development.

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“…A total of 46 proteins showed a significant change in GD patients vs. the healthy control group, 110 in GD vs. TAO, and 136 in TAO patients vs. the healthy control group. This study had the limitation of investigating only a small group of patients, namely, nine (three from each group), although it does provide new insights and potential targets for studying GD with TAO [ 43 ]. It should be emphasized that proteomics has already contributed to the significant progress made in determining which biological pathways are adversely affected in Graves’ orbitopathy ( Table 2 ).…”

Section: Markers In the Tears Of Patients With Graves’ Orbitopathymentioning

confidence: 99%

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

et al. 2022

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Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves’ disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves’ orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, there is great interest in searching for precise molecular biomarkers for early detection, disease monitoring, and clinical management. Researchers are keen to identify novel methods to predict and diagnose diseases and to monitor patient therapeutic response. Tears, due to their direct contact with the eye and the fact that lacrimal glands can also be affected by the disease, could give new insights into the mechanisms taking place in thyroid-associated orbitopathy (TAO) and reveal potential promising biomarkers. Tear fluid offers the possibility of the non-invasive acquisition of a sample with a high protein content, thereby attracting continuously growing interest in the discovery of novel biomarkers. This article provides an up-to-date overview of the various putative tear-fluid biomarkers that have been identified. In this review, we present the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases and discuss the future research directions in this area.

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Differentiation between thyroid‐associated orbitopathy and Graves’ disease by iTRAQ‐based quantitative proteomic analysis

Abstract: Differentiation between thyroid-associated orbitopathy and Graves' disease by iTRAQ-based quantitative proteomic analysis

Cited by 5 publications

References 40 publications

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

Thyroid-associated ophthalmopathy: the role of oxidative stress

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

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