Microarray analysis indicates altered expression levels of B cell genes in benign multiple sclerosis

Abstract

Objective:To identify immunological mechanisms associated with disease progression in multiple sclerosis (MS).Background:Benign MS (B-MS) is characterized with preserved motor, sensory and visual functions despite prolonged disease duration. Molecular mechanisms underlying B-MS are poorly understood.Design/Methods:Peripheral blood mononuclear cells (PBMC) obtained from 6 B-MS patients (EDSS<3.0 at disease duration > 10 years), 5 age/gender-matched non-benign MS (NB-MS) patients (EDSS≥3.0 at disease duration > 10 years) and 5 healthy controls were investigated with gene expression microarray analysis using Sureprint G3 Human Gene Expression V3 microarray system and a total of 26083 Entrez genes were evaluated. ANOVA test was used to identify genes, expression levels of which were specifically altered in B-MS patients. Gene set enrichment analysis was performed using the DAVID algorithm to analyze the biological functions of the filtered phenotypic differential genes and the results were annotated in the GEGG and GO databases. Validation of microarray study was done by real time PCR.Results:The most significantly altered expression levels belonged to factors involved in B cell proliferation (BANK1, BLNK, EBI3, BLK) and lymphocyte trafficking (CCL16, CCL19). Real time PCR studies conducted with PBMS of 30 each B-MS patients, NB-MS patients and healthy controls showed significantly reduced expression levels of BLNK, CCL16 and CCL19 genes and increased levels of BANK1, EBI3 and BLK in B-MS patients.Conclusions:B-MS patients appear to upregulate B cell development inhibitors (BANK1, EBI3, BLK) and suppress B cell development promoter BLNK and lymphocyte trafficking chemokines CCL16 and CCL19. Thus our results suggest that altered B cell functions are involved in progression of disability in MS.