Higher Levels of Plasma Fetuin-A, Nrf2, and Cytokeratin 18 in Patients with Hashimoto's Disease.

Abstract

Fetuin-A is a protein that exhibits proatherogenic, pro-inflammatory, and anti-inflammatory effects with increased insulin resistance and adipocyte dysfunction. The nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that is crucial for protecting cells against oxidative damage. As a cell death product, cytokeratin 18 (CK18) levels increase during necrosis and apoptosis of both normal and tumor cells. We analyzed the plasma levels of three biomarkers based on the hypothesis that they might be related to some pathophysiological pathways in Hashimoto's disease. We compared 34 female patients with overt hypothyroidism due to Hashimoto's disease (Group 1) with 34 age-matched healthy females (Group 2). For comparison, plasma levels of thyroid-stimulating hormone (TSH), fetuin-A, Nrf2, and CK18 were measured in all participants. In group 1, the mean TSH levels (31.4±15.3) were significantly higher than those in group 2 (2.6±1.0) (p<0.001). The levels of mean fetuin-A (606.7±34.2) and Nrf2 (1.3±0.6) were found to be significantly higher in group 1 than in group 2 (440.0±34.2 vs. 0.7±0.2) (p<0.001 for both). CK18 levels in group 1 (0.36±0.13) were also significantly higher than in group 2 (0.26±0.16) (p=0.020). A significant correlation was observed between TSH levels and fetuin-A (r=0.401, p=0.001). Increased levels of fetuin-A, Nrf2, and CK18 may be a consequence or cause of the pathophysiological pathways of Hashimoto's disease. The clinical significance of increased levels of these biomarkers requires further investigation.