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May 2018; 5 (3) ArticleOpen Access

Thymectomy lowers the myasthenia gravis biomarker miR-150-5p

Carl Johan Molin, Liis Sabre, Cleo-Aron Weis, Tanel Punga, Anna Rostedt Punga
First published March 1, 2018, DOI: https://doi.org/10.1212/NXI.0000000000000450
Carl Johan Molin
From the Department of Neuroscience, Clinical Neurophysiology (C.J.M., L.S., A.R.P.), Uppsala University, Sweden; Institute of Pathology (C.-A.W.), University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany; and Department of Medical Biochemistry and Microbiology (T.P.), Uppsala University, Sweden.
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Liis Sabre
From the Department of Neuroscience, Clinical Neurophysiology (C.J.M., L.S., A.R.P.), Uppsala University, Sweden; Institute of Pathology (C.-A.W.), University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany; and Department of Medical Biochemistry and Microbiology (T.P.), Uppsala University, Sweden.
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Cleo-Aron Weis
From the Department of Neuroscience, Clinical Neurophysiology (C.J.M., L.S., A.R.P.), Uppsala University, Sweden; Institute of Pathology (C.-A.W.), University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany; and Department of Medical Biochemistry and Microbiology (T.P.), Uppsala University, Sweden.
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Tanel Punga
From the Department of Neuroscience, Clinical Neurophysiology (C.J.M., L.S., A.R.P.), Uppsala University, Sweden; Institute of Pathology (C.-A.W.), University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany; and Department of Medical Biochemistry and Microbiology (T.P.), Uppsala University, Sweden.
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Anna Rostedt Punga
From the Department of Neuroscience, Clinical Neurophysiology (C.J.M., L.S., A.R.P.), Uppsala University, Sweden; Institute of Pathology (C.-A.W.), University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany; and Department of Medical Biochemistry and Microbiology (T.P.), Uppsala University, Sweden.
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Citation
Thymectomy lowers the myasthenia gravis biomarker miR-150-5p
Carl Johan Molin, Liis Sabre, Cleo-Aron Weis, Tanel Punga, Anna Rostedt Punga
Neurol Neuroimmunol Neuroinflamm May 2018, 5 (3) e450; DOI: 10.1212/NXI.0000000000000450

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Abstract

Objective The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels.

Methods Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18–65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II–IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+).

Results Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001).

Conclusions Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.

Glossary

AChR=
acetylcholine receptor;
ANCOVA=
analysis of covariance;
cDNA=
complementary DNA;
EOMG=
early-onset myasthenia gravis;
EV=
extracellular vesicle;
LPF=
low-power field;
miRNA=
microRNA;
MG=
myasthenia gravis;
MGTX trial=
randomized trial of thymectomy in myasthenia gravis;
qPCR=
quantitative PCR;
QMG=
quantitative MG;
TFH=
thymic lymphofollicular hyperplasia

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

  • The Article Processing Charge was funded by the authors.

  • Received October 27, 2017.
  • Accepted in final form January 30, 2018.
  • Copyright © 2018 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 License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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