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January 2019; 6 (1) ArticleOpen Access

Clinical utility of a molecular signature in inflammatory demyelinating disease

Andrew R. Pachner, Krista DiSano, Darlene B. Royce, Francesca Gilli
First published November 9, 2018, DOI: https://doi.org/10.1212/NXI.0000000000000520
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Abstract

Objective We sought to develop molecular biomarkers of intrathecal inflammation to assist neurologists in identifying patients most likely to benefit from a range of immune therapies.

Methods We used Luminex technology and index determination to search for an inflammatory activity molecular signature (IAMS) in patients with inflammatory demyelinating disease (IDD), other neuroinflammatory diagnoses, and noninflammatory controls. We then followed the clinical characteristics of these patients to find how the presence of the signature might assist in diagnosis and prognosis.

Results A CSF molecular signature consisting of elevated CXCL13, elevated immunoglobulins, normal albumin CSF/serum ratio (Qalbumin), and minimal elevation of cytokines other than CXCL13 provided diagnostic and prognostic value; absence of the signature in IDD predicted lack of subsequent inflammatory events. The signature outperformed oligoclonal bands, which were frequently false positive for active neuroinflammation.

Conclusions A CSF IAMS may prove useful in the diagnosis and management of patients with IDD and other neuroinflammatory syndromes.

Classification of evidence This study provides Class IV evidence that a CSF IAMS identifies patients with IDD.

Glossary

ADEM=
acute disseminated encephalomyelitis;
CIS=
clinically isolated syndrome;
DHMC=
Dartmouth-Hitchcock Medical Center;
IAMS=
inflammatory activity molecular signature;
IDD=
inflammatory demyelinating diseases;
IgG=
immunoglobulin G;
LP=
lumbar puncture;
NIND=
noninflammatory neurologic diseases;
OCB=
oligoclonal bands;
OIND=
other inflammatory neurologic diseases;
OIND-CNS=
OIND of the central nervous system;
OIND-PNS=
OIND of the peripheral nervous system;
PPMS=
primary progressive MS;
RIS=
radiologically isolated syndrome;
RRMS=
relapsing-remitting MS

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 authors.

  • Class of Evidence: NPub.org/coe

  • Received May 22, 2018.
  • Accepted in final form October 2, 2018.

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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