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November 2019; 6 (6) ArticleOpen Access

Elevated levels of miR-181c and miR-633 in the CSF of patients with MS

A validation study

Svenja Kramer, Arash Haghikia, Claudia Bang, Kristian Scherf, Angelika Pfanne, Alexander Duscha, View ORCID ProfileJohannes Kaisler, Barbara Gisevius, Ralf Gold, Thomas Thum, Aiden Haghikia
First published October 1, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000623
Svenja Kramer
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Arash Haghikia
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Claudia Bang
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Kristian Scherf
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Angelika Pfanne
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Alexander Duscha
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Johannes Kaisler
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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  • ORCID record for Johannes Kaisler
Barbara Gisevius
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Ralf Gold
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Thomas Thum
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Aiden Haghikia
From the Department of Neurology (S.K., A.D., J.K., B.G., R.G., Aiden Haghikia), St. Josef-Hospital, Ruhr-University Bochum; Department of Cardiology (Arash Haghikia), Campus Benjamin Franklin, Charité Universitätsmedizin-Berlin; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) (C.B., K.S., A.P., T.T.), Hannover Medical School; and REBIRTH Excellence Cluster (T.T.), Hannover Medical School, Germany.
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Citation
Elevated levels of miR-181c and miR-633 in the CSF of patients with MS
A validation study
Svenja Kramer, Arash Haghikia, Claudia Bang, Kristian Scherf, Angelika Pfanne, Alexander Duscha, Johannes Kaisler, Barbara Gisevius, Ralf Gold, Thomas Thum, Aiden Haghikia
Neurol Neuroimmunol Neuroinflamm Nov 2019, 6 (6) e623; DOI: 10.1212/NXI.0000000000000623

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Abstract

Objective To validate a previously discovered microRNA (miRNA) panel in the CSF of patients with MS, we now tested the diagnostic value of CSF-derived candidate miRNAs in a case-control study in a larger MS cohort.

Methods The levels of miR-181c, miR-633, and miR-922 were analyzed in the CSF of 218 patients with MS and 211 patients with other neurologic diseases (OND) by real-time quantitative reverse transcriptase PCR.

Results CSF levels of both miR-181c (p < 0.001 and miR-633 p < 0.001) were higher in patients with MS patients compared with patients with OND. Both miR-181c (area under the curve [AUC] 0.75, 95% CI 0.70–0.80, p < 0.001) and miR-633 (AUC 0.75, 95% CI 0.68–0.83, p < 0.001) differentiated MS from OND. Combining both miRNAs yielded a sensitivity of 62% and specificity of 89% to differentiate MS from OND. miR-922 was not confirmed to be differentially expressed in this validation cohort.

Conclusions The results of this so far largest study on CSF-based miRNAs confirm the diagnostic value of miR-181c and miR-633 for MS. The present study may help to extend the diagnostic tools for patients with suspected MS and may add further knowledge to the pathology of the disease.

Classification of Evidence This study provides Class III evidence that CSF-derived miR-181c and miR-633 distinguish patients with MS from patients with OND.

Glossary

AUC=
area under the curve;
miRNA=
microRNA;
MSR 1=
macrophage scavenger receptor 1;
NMO=
neuromyelitis optica;
OCB=
oligoclonal band;
OND=
other neurologic diseases;
PPMS=
primary progressive MS;
RR=
relative risk;
RRMS=
relapsing-remitting MS;
SPMS=
secondary progressive MS

Footnotes

  • ↵* These authors contributed equally as first authors.

  • ↵† These authors contributed equally as senior authors.

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Received March 26, 2018.
  • Accepted in final form August 20, 2019.
  • Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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