Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis.
MiRNA-181c, miRNA-633 and miRNA-922 have been reported to be deregulated in multiple sclerosis.



To investigate the association between miRNA-181c, miRNA-633 and miRNA-922 and conversion from clinically isolated syndrome (CIS) to relapsing-remitting multiple sclerosis (RRMS); and to compare microRNAs in cerebrospinal fluid (CSF) and serum with regard to dysfunction of the blood-CSF barrier.



CSF and serum miRNA-181c, miRNA-633 and miRNA-922 were retrospectively determined by quantitative real-time polymerase chain reaction in CIS patients with (CIS-RRMS) and without (CIS-CIS) conversion to RRMS within 1 year.



Thirty of 58 CIS patients developed RRMS. Cerebrospinal fluid miRNA-922, serum miRNA-922 and cerebrospinal fluid miRNA-181c were significantly higher in CIS-RRMS compared to CIS-CIS (P=0.027, P=0.048, P=0.029, respectively). High levels of cerebrospinal fluid miRNA-181c were independently associated with conversion from CIS to RRMS in multivariate Cox regression analysis (hazard ratio 2.99, 95% confidence interval 1.41-6.34, P=0.005). A combination of high cerebrospinal fluid miRNA-181c, younger age and more than nine lesions on magnetic resonance imaging showed the highest specificity (96%) and positive predictive value (94%) for conversion from CIS to RRMS. MiRNA-181c was higher in serum than in cerebrospinal fluid (P <0.001), while miRNA-633 and miRNA-922 were no different in cerebrospinal fluid and serum. Cerebrospinal fluid/serum albumin quotients did not correlate with microRNAs in cerebrospinal fluid (all P>0.711).



Cerebrospinal fluid miRNA-181c might serve as a biomarker for early conversion to RRMS. Moreover, our data suggest an intrathecal origin of microRNAs detected in the cerebrospinal fluid.
Department of Neurology, Hannover Medical School, Germany.
Jonas
J
Ahlbrecht
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Filippo
F
Martino
Department of Neurology, Hannover Medical School, Germany.
Refik
R
Pul
Department of Neurology, Hannover Medical School, Germany.
Thomas
T
Skripuletz
Department of Neurology, Hannover Medical School, Germany.
Kurt-Wolfram
KW
Sühs
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Celina
C
Schauerte
Department of Neurology, Hannover Medical School, Germany.
Özlem
Ö
Yildiz
Department of Neurology, Hannover Medical School, Germany.
Corinna
C
Trebst
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Lars
L
Tasto
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Sabrina
S
Thum
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Angelika
A
Pfanne
Department of Neurology, University of Ulm, Germany.
Romy
R
Roesler
Department of Neurology, University of Ulm, Germany.
Florian
F
Lauda
Department of Neurology, University of Rostock, Germany.
Michael
M
Hecker
Department of Neurology, University of Rostock, Germany.
Uwe K
UK
Zettl
Department of Neurology, University of Ulm, Germany.
Hayrettin
H
Tumani
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Germany.
Thomas
T
Thum
Department of Neurology, Hannover Medical School, Germany stangel.martin@mhhannover.de.
Martin
M
Stangel
D000328:Adult; D016009:Chi-Square Distribution; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
D005819:Genetic Markers; C540193:MIrn181 microRNA, human; D035683:MicroRNAs
MicroRNA; blood–cerebrospinal fluid barrier; cerebrospinal fluid; clinically isolated syndrome; conversion; multiple sclerosis