MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

PLoS One. 2017 Mar 24;12(3):e0174585. doi: 10.1371/journal.pone.0174585. eCollection 2017.

Abstract

The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / metabolism

Substances

  • MicroRNAs

Grants and funding

This work was supported by the ÚNKP-16-4-III New National Excellence Program of the Ministry of Human Capacities (http://www.kormany.hu/en/ministry-of-human-resources to GP), and the Hungarian National Scientific Research Fund (OTKA Grant No. K101470 to MZ) (http://nkfih.gov.hu/english). BLB was financially supported by the Szodoray Scholarship of the University of Debrecen, Medical Faculty (https://aok.unideb.hu/en). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.