血清角蛋白 1 与 Graves 病甲状腺功能和免疫的相关性。

Associations of serum keratin 1 with thyroid function and immunity in Graves' disease.

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Traditional Herb Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.

出版信息

PLoS One. 2023 Nov 29;18(11):e0289345. doi: 10.1371/journal.pone.0289345. eCollection 2023.

DOI:10.1371/journal.pone.0289345

PMID:38019813

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10686460/

Abstract

BACKGROUND

Autoimmune thyroid disease (AITD) can cause enormous health burdens; however, trustworthy biomarkers in identifying the onset and progression of AITD are limited. In this study, we attempted to discover new potential serum biomarkers to discriminate AITD using mass spectrometry (MS).

METHODS

In the biomarker study cohort, 20 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 20 healthy controls were enrolled for a liquid chromatographic-tandem MS assessment. A novel biomarker, keratin 1 (KRT1), was selected for further evaluation in the validation cohort, including 125 patients with GD, 34 patients with HT, and 77 controls. Relationships of serum KRT1 with AITD-related immunomodulatory cytokines were also analyzed using enzyme-linked immunosorbent assays (ELISAs).

RESULTS

In the MS analysis, KRT1 was the single marker overexpressed in GD, while it was underexpressed in HT. In the ELISA analysis of the validation cohort, KRT1 was consistently upregulated in GD, while it was not downregulated in HT. There were significant associations of KRT1 levels with thyroid function in GD, AITD, and overall subjects. Additionally, a significant association of KRT1 levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels was observed. Moreover, there were significant associations of KRT1 with osteopontin (OPN) and B-cell activating factor (BAFF) levels in GD.

CONCLUSIONS

Serum KRT1 levels were upregulated in GD and were associated with thyroid function and TSHRAb levels. Moreover, KRT1 was correlated with the BAFF and OPN levels in GD patients. Further molecular-based research to elucidate the role of KRT1 in the pathogenesis of AITD is needed.

摘要

背景

自身免疫性甲状腺疾病（AITD）会造成巨大的健康负担；然而，用于识别 AITD 发病和进展的可靠生物标志物十分有限。在本研究中，我们尝试通过质谱（MS）发现新的潜在血清生物标志物来区分 AITD。

方法

在生物标志物研究队列中，纳入 20 例格雷夫斯病（GD）患者、20 例桥本甲状腺炎（HT）患者和 20 名健康对照者进行液相色谱-串联 MS 评估。选择新型生物标志物角蛋白 1（KRT1）在包括 125 例 GD 患者、34 例 HT 患者和 77 例对照者的验证队列中进行进一步评估。还通过酶联免疫吸附测定（ELISA）分析了血清 KRT1 与 AITD 相关免疫调节细胞因子的关系。

结果

在 MS 分析中，KRT1 是 GD 中唯一过表达的标志物，而在 HT 中则表达下调。在验证队列的 ELISA 分析中，KRT1 在 GD 中持续上调，而在 HT 中并未下调。KRT1 水平与 GD、AITD 和总体患者的甲状腺功能均存在显著关联。此外，还观察到 KRT1 水平与促甲状腺激素受体抗体（TSHRAb）水平存在显著关联。此外，KRT1 与 GD 患者中的骨桥蛋白（OPN）和 B 细胞激活因子（BAFF）水平存在显著关联。