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

Abstract

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). 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). 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. 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.