Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov;159(3):618-628.
doi: 10.1111/jnc.15500. Epub 2021 Sep 15.

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real-world investigation

Igal Rosenstein  1 , Sofia Rasch  2 , Markus Axelsson  1 , Lenka Novakova  1 , Kaj Blennow  2   3 , Henrik Zetterberg  2   3   4   5   6 , Jan Lycke  1
Affiliations
Free article

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real-world investigation

Igal Rosenstein et al. J Neurochem. 2021 Nov.
Free article

Abstract

Kappa free light chain (KFLC) index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC index in MS. KFLC index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly higher KFLC index (44.6, IQR 16-128) compared with subjects with other neuro-inflammatory disorders (ONID) and symptomatic controls (SC) (2.19, IQR 1.68-2.98, p < 0.001). KFLC index had a sensitivity of 0.93 (95% CI 0.88-0.95) and specificity of 0.87 (95% CI 0.8-0.92) to discriminate CIS/RIS/MS from ONID and SC (AUC 0.94, 95% CI 0.91-0.97, p < 0.001). KFLC index and intrathecal fraction (IF) KFLC had similar accuracies to detect MS. Treatment with disease-modifying therapy (DMT) did not influence the level of KFLC index and it was not affected by demographic factors or associated with degenerative or inflammatory biomarkers in cerebrospinal fluid (CSF). KFLC index in MS diagnostics has methodological advantages compared to OCB and is independent to subjective interpretation. Moreover, it is an attractive diagnostic tool since the diagnostic specificity and sensitivity of KFLC index are similar with that of OCBs and KFLCIF and better than for IgG index. We show that KFLC index was influenced neither by DMT nor by demographic factors or other inflammatory or degenerative processes in MS as determined by biomarkers in CSF.

Keywords: Kappa free light chain index; biomarkers; cerebrospinal fluid; diagnosis; multiple sclerosis.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Andersson, M., Alvarez-Cermeno, J., Bernardi, G., Cogato, I., Fredman, P., Frederiksen, J., Fredrikson, S., Gallo, P., Grimaldi, L. M., Gronning, M., Keir, G., Lamers, K., Link, H., Magalhaes, A., Massaro, A. R., Ohman, S., Reiber, H., Ronnback, L., Schluep, M., … Wurster, U. (1994). Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. Journal of Neurology, Neurosurgery and Psychiatry, 57, 897-902. https://doi.org/10.1136/jnnp.57.8.897.
    1. Arrambide, G., & Tintore, M. (2016). CSF examination still has value in the diagnosis of MS - Commentary. Mult Scler, 22, 997-998. https://doi.org/10.1177/1352458516642033.
    1. Axelsson, M., Mattsson, N., Malmeström, C., Zetterberg, H., & Lycke, J. (2013). The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis. Journal of Neuroimmunology, 264, 100-105. https://doi.org/10.1016/j.jneuroim.2013.09.003.
    1. Blumenfeld-Kan, S., Staun-Ram, E., & Miller, A. (2019). Fingolimod reduces CXCR4-mediated B cell migration and induces regulatory B cells-mediated anti-inflammatory immune repertoire. Multiple Sclerosis and Related Disorders, 34, 29-37. https://doi.org/10.1016/j.msard.2019.06.016.
    1. Cavalla, P., Caropreso, P., Limoncelli, S., Bosa, C., Pasanisi, M. B., Schillaci, V., Alteno, A., Costantini, G., Giordana, M. T., Mengozzi, G., & Vercellino, M. (2020). Kappa free light chains index in the differential diagnosis of Multiple Sclerosis from Neuromyelitis optica spectrum disorders and other immune-mediated central nervous system disorders. Journal of Neuroimmunology, 339, 577122. https://doi.org/10.1016/j.jneuroim.2019.577122.

Publication types