Analysis of serum miRNA profiles of myasthenia gravis patients

PLoS One. 2014 Mar 17;9(3):e91927. doi: 10.1371/journal.pone.0091927. eCollection 2014.

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by the presence of autoantibodies, mainly against the acetylcholine receptor (AChR). The mechanisms triggering and maintaining this chronic disease are unknown. MiRNAs are regulatory molecules that play a key role in the immune system and are altered in many autoimmune diseases. The aim of this study was to evaluate miRNA profiles in serum of 61 AChR MG patients. We studied serum from patients with early onset MG (n = 22), late onset MG (n = 27) and thymoma (n = 12), to identify alterations in the specific subgroups. In a discovery cohort, we analysed 381 miRNA arrays from 5 patients from each subgroup, and 5 healthy controls. The 15 patients had not received any treatment. We found 32 miRNAs in different levels in MG and analysed 8 of these in a validation cohort that included 46 of the MG patients. MiR15b, miR122, miR-140-3p, miR185, miR192, miR20b and miR-885-5p were in lower levels in MG patients than in controls. Our study suggests that different clinical phenotypes in MG share common altered mechanisms in circulating miRNAs, with no additional contribution of the thymoma. MG treatment intervention does not modify the profile of these miRNAs. Novel insights into the pathogenesis of MG can be reached by the analysis of circulating miRNAs since some of these miRNAs have also been found low in MG peripheral mononuclear cells, and have targets with important roles in B cell survival and antibody production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Myasthenia Gravis / blood
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / therapy
  • Thymectomy
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • MicroRNAs

Grant support

This project was supported with a research grant from Fondo de Investigaciones Sanitarias (Fondo de Investigaciones [FIS] Intrasalud; 09/1964; principal investigator, I.I.). GNG and LQ are supported by FIS CD10/00027 and FIS CM09/00017 grants from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.