title: Analysis of serum miRNA profiles of myasthenia gravis patients.
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.
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Gisela
authors.initials: G
authors.lastname: Nogales-Gadea
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Ramos-Fransi
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Suárez-Calvet
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Navas
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-García
authors.affiliation: Department of Statistics, University of Barcelona, Barcelona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Mosquera
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Díaz-Manera
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Querol
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBER de enfermedades neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics* / Q000628:therapy; D013934:Thymectomy; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D035683:MicroRNAs