Reduced expression of the tumor necrosis factor gene in blood mononuclear cells in radiologically isolated syndrome – validation of transcriptome analysis results

Radiologically isolated syndrome (RIS) is a nosological form in which magnetic resonance imaging (MRI) reveals lesions of the white matter of the brain and/or spinal cord characteristic of multiple sclerosis (MS) in individuals in the absence of clinical symptoms of the disease. Among the studies devoted to RIS, the number of works aimed at studying the molecular mechanisms underlying its formation is very small. Previously, using next generation sequencing (NGS), we for the first time revealed significant differences in the expression profiles of several genes in peripheral blood mononuclear cells (MNCs) of individuals with RIS and healthy controls. Objective: to conduct a validation analysis of changes in the expression of the CCR2, CX3CR1, and TNF genes that were observed during NGS in the MNCs of individuals with RIS compared with healthy individuals. Patients and methods. Analysis of the expression of the CCR2, CX3CR1, and TNF genes was performed on independent validation cohorts (in MNCs of 14 subjects with RIS and 14 without RIS) by reverse transcription followed by real-time PCR. Results and discussion. In MNCs of subjects with RIS, the TNF gene expression was significantly reduced compared to healthy controls (p=0.035; FC=0.78). No significant differences in expression levels were found for other genes. Conclusion. The obtained data shows that disturbances of TNF gene expression preceding the clinical manifestations of MS, at least in individuals with RIS, which can lead to further dysregulation of several processes.