Presenter Of 1 Presentation
PS03.03 - Evidence for infection triggering mechanism in blood transcriptional profile of Radiologically isolated syndrome
Abstract
Background
The difference between Radiologically isolated syndrome (RIS) and Clinically isolated syndrome (CIS) is lack of clinical symptomatology. RIS patients have increased risk progression to CIS, however the underlying molecular mechanisms of RIS has not been yet elucidated.
Objectives
To investigate peripheral blood mononuclear cells (PBMC) transcriptional profile of patients with RIS using high throughput RNA-Seq platform.
Methods
Samples of peripheral blood mononuclear cells (PBMC) were obtained from 14 RIS subjects (9 females, 31.5±3.6 years). The comparisons were performed with 26 disease modifying drugs free CIS patients (21 females, 33.2±1.9 years, EDSS 1.0±0.2, disease duration 1.6±0.5 years) and 16 age and gender matched healthy subjects (HS). All samples were applied for PBMC transcriptome analysis using Illumina RNA-Seq technology. Differentially expressed genes (DEGs, false discovery rate≥0.1, Fold change≥1.5) were obtained using DESeq2 software and functional analysis was performed by Ingenuity Pathway Analysis software.
Results
RIS and CIS patients were characterized by 455 and 125 DEGs, respectively as compared to HS. Among CIS associated DEGs, 65 (52%) were common with RIS group. RIS transcriptional profile was enriched by genes known to be associated with inflammatory response (p=2.3E-18), including antiviral response (p=2.3E-18), antimicrobial response (p=1.9E-15), immune cell trafficking (p=5.7E-09), activation of leukocytes (p=7.1E-11), phagocytes (p=2.9E-8), antigen presenting cells (p=7.6E-08) and attraction of mononuclear leukocytes (p=1.3E-07). Moreover, the specific RIS related transcriptional profile was associated with activation of bacterial and viruses pattern recognition receptors mechanism (p=7.8E-07), interferon signaling pathway (p=1.1E-07) leading to activation of antimicrobial and antiviral mechanisms.
Conclusions
RIS subjects have common cross-disease blood transcriptional profile with CIS. RIS specific PBMC transcriptome, suggests the occurrence of an initial infection that triggers immune mechanisms operating in the preclinical stage of multiple sclerosis.