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July 2020; 7 (4) ArticleOpen Access

Analysis of soluble interleukin-2 receptor as CSF biomarker for neurosarcoidosis

Carolin Otto, Oliver Wengert, Nadine Unterwalder, Christian Meisel, Klemens Ruprecht
First published May 11, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000725
Carolin Otto
From the Department of Neurology (C.O., O.W., K.R.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Oliver Wengert
From the Department of Neurology (C.O., O.W., K.R.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Nadine Unterwalder
From the Department of Neurology (C.O., O.W., K.R.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Christian Meisel
From the Department of Neurology (C.O., O.W., K.R.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Klemens Ruprecht
From the Department of Neurology (C.O., O.W., K.R.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
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Citation
Analysis of soluble interleukin-2 receptor as CSF biomarker for neurosarcoidosis
Carolin Otto, Oliver Wengert, Nadine Unterwalder, Christian Meisel, Klemens Ruprecht
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e725; DOI: 10.1212/NXI.0000000000000725

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Abstract

Objective To systematically analyze soluble interleukin-2 receptor (sIL-2R) in CSF as a diagnostic and disease activity biomarker in patients with sarcoidosis involving the CNS (neurosarcoidosis).

Methods sIL-2R was determined by chemiluminescent immunoassays in CSF/serum samples from patients with neurosarcoidosis (n = 23), MS (n = 19), neurotuberculosis (n = 8), viral (n = 18) and bacterial (n = 9) meningitis, cerebral lymphoma (n = 15), Guillain-Barré syndrome (n = 8), and 115 patients with noninflammatory neurologic diseases (NINDs) as controls. The sIL-2R index was calculated by dividing the CSF/serum sIL-2R quotient (QsIL-2R) through the CSF/serum albumin quotient (QAlb). sIL-2R quotient diagrams were established by plotting QsIL-2R against QAlb. sIL-2R levels were correlated with clinical, MRI, and CSF disease activity markers of neurosarcoidosis.

Results Patients with neurosarcoidosis had higher CSF sIL-2R, QsIL-2R, and sIL-2R index values than patients with NINDs (p < 0.0001 for all pairwise group comparisons). sIL-2R quotient diagrams demonstrated an intrathecal sIL-2R synthesis in >50% of neurosarcoidosis samples. Similar findings were observed in viral/bacterial meningitis, CNS lymphoma, and, most pronounced, in neurotuberculosis, but not in patients with MS. CSF sIL-2R parameters were associated with clinical disease activity, leptomeningeal gadolinium enhancement, and the CSF white cell count in patients with neurosarcoidosis.

Conclusions CSF sIL-2R parameters are elevated in patients with neurosarcoidosis, but this finding is not specific for neurosarcoidosis. Nevertheless, CSF sIL-2R parameters may help distinguishing neurosarcoidosis from MS and are associated with clinical, radiologic, and CSF disease activity markers of neurosarcoidosis.

Classification of evidence This study provides Class II evidence that CSF sIL-2R parameters distinguish neurosarcoidosis from NINDs and MS.

Glossary

AUC=
area under the ROC curve;
GBS=
Guillain-Barré syndrome;
Ig=
immunoglobulin;
IL-2R=
interleukin-2 receptor;
NIND=
noninflammatory neurologic disease;
QAlb=
CSF/serum albumin quotient;
ROC=
receiver operating characteristic;
sIL-2R=
soluble interleukin-2 receptor

Footnotes

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

  • ↵* These authors contributed equally to the manuscript.

  • ↵§ These authors contributed equally to the manuscript.

  • The Article Processing Charge was funded by the authors.

  • Received November 19, 2019.
  • Accepted in final form March 26, 2020.
  • Copyright © 2020 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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Letters: Rapid online correspondence

  • Reader response: Analysis of soluble interleukin-2 receptor as CSF biomarker for neurosarcoidosis
    • Shailee S. Shah, Physician, Autoimmune Neurology and Multiple Sclerosis, Northwestern University , Northwestern Memorial Hospital; Mayo Clinic
    • Abigail McKay, APRN Certified Nurse Practitioner, Neurology, Northwestern University, Northwestern Memorial Hospital
    • Jinny Tavee, Physician, Neuromuscular, Neurology, Northwestern University, Northwestern Memorial Hospital
    Submitted May 27, 2020
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