Elevated Plasma Growth Arrest-Specific 6 Protein Levels Are Associated with the Severity of Disease During Hantaan Virus Infection in Humans.

Hemorrhagic fever with renal syndrome (HFRS) is caused by Hantaan virus (HTNV) and Seoul virus infection in Asia. The clinical manifestation of HFRS is characterized by the rapid loss of renal function (acute kidney injury) and thrombocytopenia. The specific immune mechanisms that cause thrombocytopenia in HFRS are not well described. The growth arrest-specific 6 (Gas6) protein and TAM (Tyro3, Axl and Mer) receptors have been recently shown to play prominent roles in immune regulation, and high plasma levels of Gas6 may predict the severity of diseases. The association of TAM receptors with several autoimmune diseases has been investigated, although the relationship between TAM receptors and these diseases remains unclear in HFRS. Therefore, the aim of this study was to evaluate the clinical significance of Gas6 and TAM receptor expression in HFRS. The concentrations of Gas6 in the plasma from 144 patients and the expression of TAM receptors on monocytes from 117 patients were quantified. The relationship between Gas6 levels and disease course, severity, and clinical parameters was analyzed. We first found that the plasma Gas6 levels were significantly higher in HFRS patients, whereby they were positively correlated with white blood cell counts and negatively correlated with platelet counts. The expression of Tyro3 was increased on monocytes in HFRS patients compared with that in controls. Taken together, our data indicate that elevated plasma Gas6 levels is associated with the severity of disease during HTNV infection in humans, suggesting that Gas6 may play an important role by binding with Tyro3 on monocytes, which will be assessed in future studies.