Abstract
Background
Free light chains (FLC) have been proposed as diagnostic biomarkers in the cerebrospinal fluid (CSF) of patients with inflammatory central nervous system (CNS) diseases. However, which method to use for determining an intrathecal FLC synthesis has not yet been clarified. The objective of this study was to compare the diagnostic performance of CSF FLC concentration, FLC quotient (QFLC), FLC index and FLC intrathecal fraction (FLCIF).
Methods
κ- and λ-FLC were measured by nephelometry under blinded conditions in CSF and serum sample pairs of patients with clinically isolated syndrome (CIS; n = 60), multiple sclerosis (MS; n = 60) and other neurological diseases (n = 60) from four different MS centers. QFLC was calculated as the ratio of CSF/serum FLC concentration, the FLC index as QFLC/albumin quotient and the percentage FLCIF by comparing QFLC to a previously empirically determined, albumin quotient-dependent reference limit.
Results
CSF FLC concentration, QFLC, FLC index and FLCIF of both the κ- and λ-isotype were significantly higher in patients with CIS and MS than in the control group, as well as in oligoclonal bands (OCB) positive than in OCB negative patients. Each parameter was able to identify MS/CIS patients and OCB positivity, however, diagnostic performance determined by receiver operating characteristic (ROC) analyses differed and revealed superiority of FLC index and FLCIF.
Conclusions
These findings support the diagnostic value of FLC measures that correct for serum FLC levels and albumin quotient, i.e. blood-CSF barrier function.
Author contributions: H. Hegen participated in the conception and design of the study, acquisition and statistical analysis of the data, and in drafting the manuscript. J. Walde participated in statistical analysis of the data and in reviewing the manuscript for intellectual content. D. Milosavljevic participated in acquisition of the data and in reviewing the manuscript for intellectual content. F. Aboulenein-Djamshidian participated in acquisition of the data and in reviewing the manuscript for intellectual content. M. Senel participated in acquisition of the data and in reviewing the manuscript for intellectual content. H. Tumani participated in acquisition of the data and in reviewing the manuscript for intellectual content. F. Deisenhammer participated in reviewing the manuscript for intellectual content. S. Presslauer participated in the conception and design of the study, acquisition of the data, and in reviewing the manuscript for intellectual content. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Multiple Sclerosis Society Vienna. H. Hegen participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme and Teva, and received honoraria for acting as consultant for Teva. M. Senel received honoraria for speaking and/or travel from Bayer, Biogen, Sanofi Genzyme and TEVA and research funding from the Hertha-Nathorff-Program and University of Ulm, none related to this study. H. Tumani received funding for research projects, lectures and travel from Bayer, Biogen, Genzyme, Fresenius, Merck, Mylan, Novartis, Roche, Siemens Health Diagnostics, Teva, and received research support from Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW. F. Deisenhammer participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and Teva-Ratiopharm. His institution has received financial support for participation in randomized controlled trials of INFb-1b (Betaferon, Bayer Schering Pharma), INFb-1a (Avonex, Biogen; Rebif, Merck Serono), glatiramer acetate (Copaxone, Teva Pharmaceuticals), Natalizumab (Tysabri, Biogen), in multiple sclerosis. He is section editor of the MSARD journal (Multiple Sclerosis and Related Disorders). S. Presslauer participated in meetings sponsored by Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva.
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.
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