title: Circulating miRNAs in myasthenia gravis: miR-150-5p as a new potential biomarker.
abstract: OBJECTIVE
  Myasthenia gravis (MG) is a chronic autoimmune disorder where autoantibodies target the nicotinic acetylcholine receptors (AChR+) in about 85% of cases, in which the thymus is considered to play a pathogenic role. As there are no reliable biomarkers to monitor disease status in MG, we analyzed circulating miRNAs in sera of MG patients to find disease-specific miRNAs.
  
  
  METHODS
  Overall, 168 miRNAs were analyzed in serum samples from four AChR+ MG patients and four healthy controls using Exiqon Focus miRNA polymerase chain reaction (PCR) Panel I + II. Specific accumulation pattern of 13 miRNAs from the discovery set was subsequently investigated in the sera of 16 AChR+ MG patients and 16 healthy controls. All patients were without immunosuppressive treatment. Selected specific miRNAs were further analyzed in the serum of nine MG patients before and after thymectomy to assess the effect of thymus removal on the accumulation of the candidate miRNAs in patient sera.
  
  
  RESULTS
  Three miRNAs were specifically dysregulated in AChR+ MG patient sera samples. Hsa-miR150-5p, which induces T-cell differentiation, as well as hsa-miR21-5p, a regulator of Th1 versus Th2 cell responses, were specifically elevated in MG sera. Additionally, hsa-miR27a-3p, involved in natural killer (NK) cell cytotoxicity, was decreased in MG. Hsa-miR150-5p levels had the highest association with MG and were significantly reduced after thymus removal in correlation with disease improvement.
  
  
  CONCLUSIONS
  WE PROPOSE THAT THE VALIDATED MIRNAS: hsa-miR150-5p, hsa-miR21-5p, and hsa-miR27a-3p can serve as novel serum biomarkers in AChR+ MG. Hsa-miR-150-5p could be a helpful marker to monitor disease severity.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University BMC Box 582, Uppsala, Sweden.
authors.forename: Tanel
authors.initials: T
authors.lastname: Punga
authors.affiliation: INSERM U974, CNRS UMR 7215, Institut de Myologie, UPMC Univ Paris 6 Paris, France.
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
authors.affiliation: Feldbergstrasse 67 Basel, 4057, Switzerland.
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.affiliation: INSERM U974, CNRS UMR 7215, Institut de Myologie, UPMC Univ Paris 6 Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Truffault
authors.affiliation: INSERM U974, CNRS UMR 7215, Institut de Myologie, UPMC Univ Paris 6 Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
authors.affiliation: Department of Clinical Neurophysiology, Institute of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Punga