Abstract
Objective To determine what kappa free light chain (KFLC) metric has the highest capacity to separate healthy patients from patients with MS, we evaluated the sensitivity, specificity, and the overall diagnostic accuracy of 4 different KFLC metrics. To assess the usefulness of KFLC in the diagnostics of MS, we compared the different KFLC metrics with oligoclonal bands (OCBs), the current gold standard biochemical method to demonstrate intrathecal antibody production.
Methods CSF and plasma were collected from patients with confirmed or suspected MS, other neurological diseases, as well as symptomatic and healthy controls between May 2017 and May 2018 (n = 335) at the Department of Neurology, Karolinska University Hospital, as part of routine diagnostic workup. KFLC analysis and isoelectric focusing for the detection of oligoclonal bands (OCB) were determined and correlated with diagnosis. Receiver operating characteristic (ROC) curve analysis was used to determine accuracy.
Results OCBs yielded a sensitivity of 87% and a specificity of 100%. All KFLC metrics showed a high sensitivity (89%–95%) and specificity (95%–100%). Using the optimal cutoff according to the Youden Index resulted for the KFLC intrathecal fraction in a cutoff of −0.41 with a sensitivity of 95% and a specificity of 97% and for CSF KFLC/CSF albumin with a cutoff of 1.93 × 10−3 with a sensitivity of 94% and specificity of 100%.
Conclusion All evaluated KFLC metrics have excellent accuracy, and both KFLC intrathecal fraction and CSF KFLC/CSF albumin are at least as good as OCB in separating patients with MS from a control group.
Classification of evidence This study provides Class III evidence that CSF KFLC accurately distinguishes patients with MS from healthy controls.
Glossary
- CINDC=
- central inflammatory neurologic disease control;
- CIS=
- clinically isolated syndrome;
- FLC=
- free light chain;
- HC=
- healthy control;
- IEF=
- isoelectric focusing;
- IF=
- intrathecal fraction;
- KFLC=
- kappa free light chain;
- NINDC=
- noninflammatory neurologic disease control;
- OCB=
- oligoclonal band;
- P Alb=
- plasma albumin;
- PINDC=
- peripheral inflammatory neurologic disease control;
- Q Alb=
- albumin quotient;
- SC=
- symptomatic control
Footnotes
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 December 16, 2019.
- Accepted in final form April 20, 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 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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