Exploring the role of the IL-12/IFN-γ immune axis in subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal neurological syndrome resulting from persistent measles virus infection in the central nervous system. Despite the availability of a measles vaccine, SSPE continues to pose a significant health burden, and immunogenetic risk factors remain unclear. We aimed to study the role of the interleukin 12 (IL-12)/interferon-gamma (IFN-γ) axis, known for it's significance in antiviral defense, in the development of SSPE.

This cross-sectional case-control study recruited consecutive age and sex-matched SSPE cases (n = 51) and controls (n = 51). Gene expressions were quantified for IL-12B, IFNG, IL-12RB1, STAT4, IFNGR1, IFNGR2, STAT1, IRF8, and ISG15 genes using quantitative realtime PCR. Additionally, plasma levels of IL-12p40, IL-12p70, and IFN-γ were measured using the multiplex suspension array platform. Furthermore, single nucleotide polymorphisms (SNPs) in IL-12B, IL-12RB1, IFNG, IFNGR1, IFNGR2, and ISG15 genes were examined using TaqMan SNP genotyping assays. Statistical analyses compared gene expressions, cytokine levels, and alleles and genotypes frequencies between SSPE patients and controls.

Significant alterations in the expression of key IL-12 pathway-related genes were observed in SSPE patients compared to controls, including lower STAT4 (p = 0.0445) and higher IFNGR1 (p = 0.0005) and IRF8 (p = 0.0229). Elevated plasma levels of IL-12p70 (p = 0.0015) and IFN-γ (p = 0.0381) were also observed in SSPE patients. Additionally, associations with SSPE were found for the rs3212227 SNP in IL-12B (p = 0.048), the rs1059293 SNP in IFNGR2 (p = 0.052), and the rs1921 SNP in ISG15 (p = 0.054) genes. Notably, gene-gene interactions among these genes exhibited associations with SSPE.

This study provides novel insights into the dysregulation of the IL-12/IFN-γ immune axis in SSPE and underscores the complex interplay between host genetics and viral infection in disease pathogenesis.