Genome wide differences of gene expression associated with HLA-DRB1 genotype in multiple sclerosis: A pilot study

Using two microarray platforms, we identify HLA-DRB5 as the most highly expressed gene in MS compared to healthy subjects. As expected, HLA-DRB5 expression was associated with the HLA-DRB1*1501 MS susceptibility allele. Besides HLA-DRB5, there were 1219 differentially expressed exons (p < 0.01, |fold change (FC)| > 1.2) that differed between HLA-DRB1*1501 Positive multiple sclerosis subjects (MSP) compared to HLA-DRB1*1501 negative multiple sclerosis subjects (MSN). Analysis of the regulated genes revealed significantly different immune signaling pathways including IL-4 and IL-17 in these two MS genotypes. Different risk alleles appear to be associated with different patterns of gene expression that may reflect differences in pathophysiology of these two MS subtypes. These preliminary data will need to be confirmed in future studies.

► We identified different patterns of MS gene expression based on HLA risk allele. ► Allele+ MS has up regulated genes in the IL-17, Notch and CDK signaling pathways. ► Allele- MS had up regulated genes in the complement and IL-4 signaling pathways. ► Allele+ and allele- MS had up regulated genes in common with rheumatoid arthritis.