ABSTRACT
Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-sequencing profiles from sorted blood immune CD4+ and CD8+ T cells, CD14+ monocytes and CD19+ B cells from healthy controls (HCs) and MS patients. Results: We identified differentially accessible regions between MS patients and HCs, primarily in CD4+ and CD19+. CD4+ regions were enriched for MS-associated single nucleotide polymorphisms and differentially methylated loci. In the vicinity of differentially accessible regions of CD4+ cells, 42 differentially expressed genes were identified. The top two dysregulated genes identified in this multilayer analysis were CCDC114 and SERTAD1. Conclusion: These findings provide new insight into the primary role of CD4+ and CD19+ cells in MS.
Lay abstract Multiple sclerosis (MS) is a devastating disease that affects individuals at a young age and gradually worsens over their lifespan. Currently, treatment for MS is broad, meaning it treats the symptoms but not the cause of the disease. Treating symptoms means that patients may feel better, but their general quality of life is not normal. In addition, treating symptoms can lead to the underlying cause still being present, which can come back once treatment is stopped. What we are striving to do in this article is to better understand the cause. If we can do that, we can have targeted treatment that will get rid of the disease without the fear of it coming back and drastically improve quality of life and life span. Here, we have identified the complex nature of MS and made an effort to identify certain genes that are different in MS patients and present a way to better understand MS using advanced genome study methodologies.
