title: Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity.
abstract: MicroRNAs (miRNAs) are promising multiple sclerosis (MS) biomarkers. Establishing the association between miRNAs and magnetic resonance imaging (MRI) measures of disease severity will help define their significance and potential impact.
  
  
  
  To correlate circulating miRNAs in the serum of patients with MS to brain and spinal MRI.
  
  
  
  A cross-sectional study comparing serum miRNA samples with MRI metrics was conducted at a tertiary MS referral center. Two independent cohorts (41 and 79 patients) were retrospectively identified from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital. Expression of miRNA was determined by locked nucleic acid-based quantitative real-time polymerase chain reaction. Spearman correlation coefficients were used to test the association between miRNA and brain lesions (T2 hyperintense lesion volume [T2LV]), the ratio of T1 hypointense lesion volume [T1LV] to T2LV [T1:T2]), brain atrophy (whole brain and gray matter), and cervical spinal cord lesions (T2LV) and atrophy. The study was conducted from December 2013 to April 2016.
  
  
  
  miRNA expression.
  
  
  
  Of the 120 patients included in the study, cohort 1 included 41 participants (7 [17.1%] men), with mean (SD) age of 47.7 (9.5) years; cohort 2 had 79 participants (26 [32.9%] men) with a mean (SD) age of 43.0 (7.5) years. Associations between miRNAs and MRIs were both protective and pathogenic. Regarding miRNA signatures, a topographic specificity differed for the brain vs the spinal cord, and the signature differed between T2LV and atrophy/destructive measures. Four miRNAs showed similar significant protective correlations with T1:T2 in both cohorts, with the highest for hsa.miR.143.3p (cohort 1: Spearman correlation coefficient rs = -0.452, P = .003; cohort 2: rs = -0.225, P = .046); the others included hsa.miR.142.5p (cohort 1: rs = -0.424, P = .006; cohort 2: rs = -0.226, P = .045), hsa.miR.181c.3p (cohort 1: rs = -0.383, P = .01; cohort 2: rs = -0.222, P = .049), and hsa.miR.181c.5p (cohort 1: rs = -0.433, P = .005; cohort 2: rs = -0.231, P = .04). In the 2 cohorts, hsa.miR.486.5p (cohort 1: rs = 0.348, P = .03; cohort 2: rs = 0.254, P = .02) and hsa.miR.92a.3p (cohort 1: rs = 0.392, P = .01; cohort 2: rs = 0.222, P = .049) showed similar significant pathogenic correlations with T1:T2; hsa.miR.375 (cohort 1: rs = -0.345, P = .03; cohort 2: rs = -0.257, P = .022) and hsa.miR.629.5p (cohort 1: rs = -0.350, P = .03; cohort 2: rs = -0.269, P = .02) showed significant pathogenic correlations with brain atrophy. Although we found several miRNAs associated with MRI outcomes, none of these associations remained significant when correcting for multiple comparisons, suggesting that further validation of our findings is needed.
  
  
  
  Serum miRNAs may serve as MS biomarkers for monitoring disease progression and act as surrogate markers to identify underlying disease processes.
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Keren
authors.initials: K
authors.lastname: Regev
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Biostatistics Center, Massachusetts General Hospital, Boston.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Fariha
authors.initials: F
authors.lastname: Khalid
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Anu
authors.initials: A
authors.lastname: Paul
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Renxin
authors.initials: R
authors.lastname: Chu
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Subhash
authors.initials: S
authors.lastname: Tummala
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Camilo
authors.initials: C
authors.lastname: Diaz-Cruz
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Radhika
authors.initials: R
authors.lastname: Raheja
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mazzola
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Felipe
authors.initials: F
authors.lastname: von Glehn
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pia
authors.initials: P
authors.lastname: Kivisakk
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sheena L
authors.initials: SL
authors.lastname: Dupuy
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Gloria
authors.initials: G
authors.lastname: Kim
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Roopali
authors.initials: R
authors.lastname: Gandhi
authors.affiliation: Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts4Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000000981:diagnostic imaging; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy*; D012333:RNA, Messenger / Q000097:blood; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000473:pathology; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger