A subtype of multiple sclerosis defined by an activated immune defense program

Abstract

Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age-and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.

Molecular subtypes of systemic sclerosis in association with anti-centromere antibodies and digital ulcers

“…Upregulation of type I IFN-induced genes has been reported for PB cells of (a subset) patients with other autoimmune diseases, such as systemic lupus erythematosus (SLE), [10][11][12][13] rheumatoid arthritis, 14 dermatomyositis 15 multiple sclerosis, 16 and for tissues of patients with Sjogren's syndrome. 17 Type I IFNs are early mediators of the innate immune response that influence the adaptive immune response through direct and indirect actions on dendritic cells, T and B cells, and natural killer cells.…”

“…This is different from the observation made for differential IFN type I response gene expression in SLE and other autoimmune diseases. 10,14,16 Table 2). After distribution analysis, statistical differences between patients and healthy controls per IFN type were tested by Student's t-test (NS, nonsignificant).…”

“…16 In short, total RNA was isolated from PB using the PAXgene RNA isolation kit according to the manufacturer's instructions, including a DNAse step to remove contaminating genomic DNA (Qiagen, Venlo, The Netherlands). Total RNA (1 mg) was linearly amplified using the MessageAmp Amplification kit (Ambion, Huntingdon, UK).…”

Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

“…stanford.edu//) as described previously. 32 Raw (log2) data can be downloaded from the publicly accessible Stanford database website. To determine the significant pharmacological response to treatment, we performed a paired analysis using significance analysis of microarrays.…”

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

“…There is little doubt that multiple sclerosis (MS) is an immune‐mediated disease 17, 18, 19. We therefore use this disease as a positive control with regard to expected enrichment in heritability for annotations from immune cells.…”