Altered Expression of B Cell Receptor Signaling Pathway Genes in Peripheral Blood of Patients with Multiple Sclerosis

Shirin Jalili; Hadi Shirzad; Seyed Amin  Mousavi Nezhad

doi:10.18502/ijaai.v23i2.15324

Shirin Jalili Institute of Police Equipment and Technologies, Policing Sciences and Social Studies Research Institute, Tehran, Iran
Hadi Shirzad Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran
Seyed Amin Mousavi Nezhad Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v23i2.15324

Keywords: B cell; B cell receptor signaling pathway; Gene expression; Multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease and has adverse implications. The exact mechanism of its pathogenesis is not fully understood and remains to be elucidated. In the current study we aimed to identify key genes that can serve as potential biomarkers and therapeutic targets for MS and shed light on pathogenesis mechanisms involved in MS.

We analyzed a gene expression dataset (GES21942) and found 266 differentially expressed genes (DEGs) including 183 upregulated and 83 downregulated genes in MS patients compared to controls. Then we conducted pathway enrichment on DEGs and selected the top enriched pathway i.e., B cell receptor signaling pathway, and 5 genes of this pathway (CR2, BLK, BLNK, RASGRP3, and KRAS) for further investigation in our clinical samples. We recruited 50 MS patients and 50 controls and assessed the expression of selected genes in the circulation of patients versus controls.

Expression of CR2, BLK, BLNK, and RASGRP3 were significantly higher in MS cases compared with controls. There was no significant difference in expression of KRAS between patients and controls. All of the selected genes with differential expression had noticeable diagnostic power and CR2 was the most robust gene in differentiating MS cases from controls. Additionally, a combination of genes resulted in enhanced diagnostic power.

Collectively our results suggest that the B cell receptor signaling pathway and the selected genes from this pathway may be implicated in the pathogenesis of MS and each of these genes can be considered as potential diagnostic biomarkers and therapeutic targets.