title: Circulating microRNAs as biomarkers for rituximab therapy, in neuromyelitis optica (NMO).
abstract: Neuromyelitis optica (NMO) is a chronic autoimmune disease of the central nervous system (CNS). The main immunological feature of the disease is the presence of autoantibodies to Aquaporin 4 (AQP4+), identified in about 82 % of cases. Currently, there are no reliable biomarkers for monitoring treatment response in patients with NMO. In an effort to identify biomarkers, we analyzed microRNAs (miRNAs) in the blood of rituximab-treated NMO patients before and after therapy.
  
  
  
  Total RNA extracted from whole blood of nine rituximab-responsive NMO patients before and 6 months following treatment was subjected to small RNAseq analysis. The study included an additional group of seven untreated AQP4+ seropositive NMO patients and 15 healthy controls (HCs).
  
  
  
  Fourteen miRNAs were up regulated and 32 were downregulated significantly in the blood of NMO patients following effective therapy with rituximab (all p < 0.05). Furthermore, we show that expression of 17 miRNAs was significantly higher and of 25 miRNAs was significantly lower in untreated NMO patients compared with HCs (all p < 0.05). Following rituximab treatment, the expression levels of 10 of the 17 miRNAs that show increased expression in NMO reverted to the levels seen in HCs. Six of these "normalized" miRNAs are known as brain-specific/enriched miRNAs.
  
  
  
  Specific miRNA signatures in whole blood of patients with NMO might serve as biomarkers for therapy response. Furthermore, monitoring the levels of brain-specific/enriched miRNAs in the blood might reflect the degree of disease activity in the CNS of inflammatory demyelinating disorders.
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel. adembinsky@gmail.com.
authors.forename: Adi
authors.initials: A
authors.lastname: Vaknin-Dembinsky
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Charbit
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Livnat
authors.initials: L
authors.lastname: Brill
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.affiliation: Nephrology and Hypertension Services, Internal Medicine Wing, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Devorah
authors.initials: D
authors.lastname: Gur-Wahnon
authors.affiliation: Nephrology and Hypertension Services, Internal Medicine Wing, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Iddo Z
authors.initials: IZ
authors.lastname: Ben-Dov
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.|Department of Neurology, the Agnes-Ginges Center for Neurogenetics and Leslie and Michel Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Medical Center, Ein-Karem, Jerusalem, 91120, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Lavon
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000069283:Rituximab / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D035683:MicroRNAs; D000069283:Rituximab
keywords: Aquaporin 4 (AQP4); Brain-specific microRNAs; Circulating biomarkers; Neuromyelitis optica (NMO); Rituximab