To investigate the expression and clinical significance of interferon gamma inducible protein 16 (IFI16) and stimulator of interferon genes (STING) of children with hand, foot and mouth disease (HFMD) infected by Coxsackie virus A6 (CV-A6).

The peripheral blood samples of 55 children with CV-A6 HFMD admitted to the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Children’s Hospital and Xi’an Central Hospital from May to August 2023 were collected, and 20 samples were collected from healthy children as controls. According to the severity of the disease, the children were divided into mild and severe cases. Enzyme-linked immunosorbent (ELISA) assay was used to detect the expression levels of IFI16, Cyclic GMP-AMP Synthase (cGAS), STING, interferon regulatory factor 3 (IRF-3) and interferon-α (IFN-α) in different severity, acute phase and recovery phase.

Compared with control group, the expression of IFI16 and STING increased in mild CV-A6 HFMD children, and decreased in severe CV-A6 HFMD children [15.92 (13.34, 19.13) ng/ml vs. 13.66 (11.91, 14.83) ng/ml: Z =-2.200, P = 0.028; 1 345.45 (991.55, 1 843.63) pg/ml vs. 1 072.26 (947.25, 1 180.97) pg/ml: Z =-2.000, P = 0.046]. Only the expression of STING in children with severe CV-A6 HFMD was significantly different between the acute stage and the recovery stage [1 072.26 (947.25, 1 180.97) vs. 1 665.29 (1 341.62, 1 961.83): Z =-3.237, P = 0.001]. Compared with the control group, the expression of IFN-α in the mild CV-A6 HFMD group decreased [864.47 (721.41, 952.89) pg/ml vs. 715.08 (575.41, 896.69) pg/ml: Z =-2.054, P = 0.040]. There was no significant difference in the expression of cGAS and IRF3 among the control group, mild HFMD group and severe HFMD group (all P > 0.05). Sperman correlation analysis showed that IFI16 expression was positively correlated with STING expression (r = 0.286, P = 0.013). The expression of IFI16 (Z =-3.307, P = 0.001) and STING (Z =-2.702, P = 0.007) in children with nerve involvement (positive pathological reflex) were lower than those in children with negative pathological reflex. Children with limb twitching (Z =-2.489, P = 0.013), poor mental state (Z =-2.542, P = 0.011), and high blood glucose level (Z =-2.828, P = 0.005) also had lower IFI16 levels than those without such characteristics, and IFI16 was negatively correlated with blood glucose levels (Sperman correlation analysis: r =-0.427, P = 0.001).

CV-A6 infection can activate the IFI16-STING pathway. The expression of IFI16 and STING are associated with the severity of CV-A6-induced HFMD, and their higher expression levels may be a protective factor of the body against the progression to severe disease.