Abstract
Background:
The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation.
Methods:
A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method.
Results:
The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%).
Conclusions:
KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Leray E, Moreau T, Fromont A, Edan G. Epidemiology of multiple sclerosis. Rev Neurol (Paris) 2016;172:3–13.10.1016/j.neurol.2015.10.006Search in Google Scholar PubMed
2. Hurwitz BJ. The diagnosis of multiple sclerosis and the clinical subtypes. Ann Indian Acad Neurol 2009;12:226–30.10.4103/0972-2327.58276Search in Google Scholar PubMed PubMed Central
3. McDonald WI, Compston A, Edan G, Goodkin D, Hartung H-P, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121–7.10.1002/ana.1032Search in Google Scholar PubMed
4. Koriem KM. Multiple sclerosis: new insights and trends. Asian Pac J Trop Biomed 2016;6:429–40.10.1016/j.apjtb.2016.03.009Search in Google Scholar
5. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302.10.1002/ana.22366Search in Google Scholar PubMed PubMed Central
6. Presslauer S, Milosavljevic D, Brücke T, Bayer P, Hübl W, Hübl W. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol 2008;255:1508–14.10.1007/s00415-008-0954-zSearch in Google Scholar PubMed
7. Presslauer S, Milosavljevic D, Huebl W, Aboulenein-Djamshidian F, Krugluger W, Deisenhammer F, et al. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: a multicenter study. Mult Scler Houndmills Basingstoke Engl 2016;22:502–10.10.1177/1352458515594044Search in Google Scholar PubMed
8. Franciotta D, Lolli F. Interlaboratory reproducibility of isoelectric focusing in oligoclonal band detection. Clin Chem 2007;53:1557–8.10.1373/clinchem.2007.089052Search in Google Scholar PubMed
9. Duranti F, Pieri M, Centonze D, Buttari F, Bernardini S, Dessi M. Determination of κFLC and κ index in cerebrospinal fluid: a valid alternative to assess intrathecal immunoglobulin synthesis. J Neuroimmunol 2013;263:116–20.10.1016/j.jneuroim.2013.07.006Search in Google Scholar PubMed
10. Hassan-Smith G, Durant L, Tsentemeidou A, Assi LK, Faint JM, Kalra S, et al. High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis. J Neuroimmunol 2014;276:175–9.10.1016/j.jneuroim.2014.08.003Search in Google Scholar PubMed
11. Zeman D, Kušnierová P, Švagera Z, Všianský F, Byrtusová M, Hradílek P, et al. Assessment of intrathecal free light chain synthesis: comparison of different quantitative methods with the detection of oligoclonal free light chains by isoelectric focusing and affinity-mediated immunoblotting. PLoS One 2016;11:e0166556.10.1371/journal.pone.0166556Search in Google Scholar PubMed PubMed Central
12. Goffette S, Schluep M, Henry H, Duprez T, Sindic CJ. Detection of oligoclonal free kappa chains in the absence of oligoclonal IgG in the CSF of patients with suspected multiple sclerosis. J Neurol Neurosurg Psychiatry 2004;75:308–10.10.1136/jnnp.2003.010710Search in Google Scholar PubMed PubMed Central
13. Petzold A. Intrathecal oligoclonal IgG synthesis in multiple sclerosis. J Neuroimmunol 2013;262:1–10.10.1016/j.jneuroim.2013.06.014Search in Google Scholar PubMed
14. Senel M, Tumani H, Lauda F, Presslauer S, Mojib-Yezdani R, Otto M, et al. Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis. PLoS One 2014;9:e88680.10.1371/journal.pone.0088680Search in Google Scholar PubMed PubMed Central
©2018 Walter de Gruyter GmbH, Berlin/Boston
