Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis

作者：Ahlbrecht Jonas; Martino Filippo; Pul Refik; Skripuletz Thomas; Suehs Kurt Wolfram; Schauerte Celina; Yildiz Oezlem; Trebst Corinna; Tasto Lars; Thum Sabrina; Pfanne Angelika; Roesler Romy; Lauda Florian; Hecker Michael; Zettl Uwe K; Tumani Hayrettin; Thum Thomas; Stangel Martin^*

来源：Multiple Sclerosis, 2016, 22(9): 1202-1214.

DOI：10.1177/1352458515613641

• MicroRNA
• multiple sclerosis
• clinically isolated syndrome
• cerebrospinal fluid
• conversion
• blood-cerebrospinal fluid barrier

Background: MiRNA-181c, miRNA-633 and miRNA-922 have been reported to be deregulated in multiple sclerosis.
Objectives: 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.
Methods: 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.
Results: 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).
Conclusions: 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.

• 出版日期2016-8