Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells

Neuromolecular Med. 2020 Mar;22(1):111-120. doi: 10.1007/s12017-019-08570-6. Epub 2019 Oct 1.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that degenerates the central nervous system (CNS). B cells exacerbate the progression of CNS lesions in MS by producing auto-antibodies, pro-inflammatory cytokines, and presenting auto-antigens to activated T cells. Long non-coding RNAs (lncRNAs) play a crucial role in complex biological processes and their stability in body fluids combined with their tissue specificity make these biomolecules promising biomarker candidates for MS diagnosis. In the current study, we investigated memory B cell-specific lncRNAs located, on average, less than 50 kb from differentially expressed protein-coding genes in MS patients compared to healthy individuals. Moreover, we included in our selection criteria lncRNA transcripts predicted to interact with microRNAs with established involvement in MS. To assess the expression levels of lncRNAs and their adjacent protein-coding genes, quantitative reverse transcription PCR was performed on peripheral blood mononuclear cells samples of 50 MS patients compared to 25 controls. Our results showed that in relapsing MS patients, compared to remitting MS patients and healthy controls, lncRNA RP11-530C5.1 was up-regulated while AL928742.12 was down-regulated. Pearson's correlation tests showed positive correlations between the expression levels of RP11-530C5.1 and AL928742.12 with PAWR and IGHA2, respectively. The results of the ROC curve test demonstrated the potential biomarker roles of AL928742.12 and RP11-530C5.1. We conclude that these lncRNAs are potential markers for detection of relapsing MS patients.

Keywords: Biomarker; Multiple sclerosis; PBMC; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • B-Lymphocyte Subsets / immunology*
  • Biomarkers
  • Case-Control Studies
  • Cell Lineage
  • Computer Simulation
  • Disability Evaluation
  • Female
  • Gene Expression Regulation
  • Gene Ontology
  • Humans
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Heavy Chains / genetics
  • Immunologic Memory / immunology*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / therapeutic use
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Immunoglobulin Heavy Chains
  • RNA, Long Noncoding
  • prostate apoptosis response-4 protein