Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Abstract

Objective: To explore which pattern recognition receptors (PRRs) play a key role in the development of hand, foot, and mouth disease (HFMD) by analyzing PRR-associated genes. Methods: We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells (PBMCs) infected with enterovirus 71 (EV-A71) which were derived from patients with HFMD of different severities and at different stages. A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates. Subsequently, ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes, specifically, BST2, IRF7, 1FI16, TRIM21, MX1, and DDX58. Results: Compared with those at the recovery stage, the expression levels of BST2 (P=0.027), IFI16 (P=0.016), MX1 (P=0.046) and DDX58 (P=0.008) in the acute stage of infection were significantly upregulated, while no significant difference in the expression levels of IRF7 (P=0.495) and TRIM21 (P=0.071) was found between different stages of the disease. The expression levels of BST2, IRF7, IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens, and BST2, IRF7, IFI16 and MX1 expression levels were significantly lower in coxsackie B virus (COXB) positive patients than the negative patients. Expression levels of one or more of BST2, IRF7, IFI16, TRIM21, MX1 and DDX58 genes were correlated with PCT levels, various white blood cell counts, and serum antibody levels that reflect disease course of HFMD. Aspartate aminotransferase was correlated with BST2, MX1 and DDX58 expression levels. Conclusions: PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.