Multiple Sclerosis Journal - October 2017 - 1496

681503
research-article2016

MSJ0010.1177/1352458516681503Multiple Sclerosis JournalMM Voortman, T Stojakovic

MULTIPLE
SCLEROSIS
JOURNAL

MSJ

Original Research Paper

Prognostic value of free light chains lambda
and kappa in early multiple sclerosis
Margarete M Voortman, Tatjana Stojakovic, Lukas Pirpamer, Margit Jehna,
Christian Langkammer, Hubert Scharnagl, Markus Reindl, Stefan Ropele, Thomas Seifert-Held,
Juan-Jose Archelos, Siegrid Fuchs, Christian Enzinger, Franz Fazekas and Michael Khalil

Abstract
Background: Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested
as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly
in early stages.
Objective: To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS.
Methods: We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry
in 61 patients (CIS (n = 48), relapsing-remitting multiple sclerosis (n = 13)) and 60 non-inflammatory
neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR),
1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up
(median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent
brain volume change (PBVC).
Results: CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower
KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were
found for FLC variables with T2LL or PBVC.
Conclusion: Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports
their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS
beyond OCB.
Keywords: Multiple sclerosis, magnetic resonance imaging, immunoglobulin kappa chains, immunoglobulin
lambda chains, prognosis, cerebrospinal fluid, serum
Date received: 23 June 2016; revised: 23 September 2016; accepted: 31 October 2016
Introduction
The presence of immunoglobulin (Ig) G oligoclonal
bands (OCB) in cerebrospinal fluid (CSF) is known to
support a diagnosis of multiple sclerosis (MS)
although such evidence is not included in current
diagnostic criteria except for primary progressive
MS.1 Measuring the levels of CSF Ig free light chains
(FLC) kappa (KFLC) and lambda (LFLC) has been
proposed as a potential alternative to the qualitative
assessment of OCB and showed comparable diagnostic sensitivity and specificity.2-8 The presence of OCB
has also been associated with a higher risk of conversion from a clinically isolated syndrome (CIS) to

1496

clinically definite multiple sclerosis (CDMS)9,10 and
disease progression.3
To what extent a quantification of FLC may also add
information in predicting progression of MS was yet
investigated only in a few studies.3,11,12 In one of
them, KFLC have been associated with conversion
from CIS to CDMS. However, in that study a substantial number of non-converters were OCB negative.11
Thus, the observed contribution of KFLC could have
mirrored just the predictive capacity of OCB and not
necessarily indicates a predictive role of KFLC on
their own. Furthermore, most studies focused solely

Multiple Sclerosis Journal
2017, Vol. 23(11) 1496-1505
DOI: 10.1177/
https://doi.org/10.1177/1352458516681503
1352458516681503
https://doi.org/10.1177/1352458516681503
© The Author(s), 2016.
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Correspondence to:
M Khalil
Department of Neurology,
Medical University of
Graz, Auenbruggerplatz 22,
A-8036 Graz, Austria.
michael.khalil@
medunigraz.at
Margarete M Voortman
Lukas Pirpamer
Christian Langkammer
Stefan Ropele
Thomas Seifert-Held
Juan-Jose Archelos
Siegrid Fuchs
Franz Fazekas
Michael Khalil
Department of Neurology,
Medical University of Graz,
Graz, Austria
Tatjana Stojakovic
Hubert Scharnagl
Clinical Institute of Medical
and Chemical Laboratory
Diagnostics, Medical
University of Graz, Graz,
Austria
Margit Jehna
Division of Neuroradiology,
Vascular and Interventional
Radiology, Medical
University of Graz, Graz,
Austria
Markus Reindl
Clinical Department
of Neurology, Medical
University of Innsbruck,
Innsbruck, Austria
Christian Enzinger
Department of Neurology,
Medical University of Graz,
Graz, Austria/Division of
Neuroradiology, Vascular
and Interventional Radiology,
Medical University of Graz,
Graz, Austria

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