Multiple Sclerosis Journal - October 2017 - 1503

MM Voortman, T Stojakovic et al.
neurological controls) were associated with faster
conversion to CDMS.11 Notably, the patient group
designated as 'low' KFLC in this report consisted of
86% OCB-negative patients, which needs to be taken
into consideration when interpreting these data. A
recent study assessing CIS patients over 2 years found
significantly higher CSF levels of both KFLC and
LFLC in CIS-MS converters (n = 98) compared to
CIS non-converters (n = 41).13 Also here, the non-converter group consisted of significantly more OCBnegative patients than the converters (51% and 7%,
respectively, p < 0.0001).
Contrarily, in this study, we aimed to test whether a
quantitative measure, like CSF FLC might yield additional information against the background of already
existing OCB positivity, which eradicates a potential
confounding effect. Thus, we here embarked on studying exclusively OCB positive CIS/MS patients.
The KFLC/LFLC serum ratio has been shown to be
prognostic in several diseases, for example, monoclonal gammopathies32 and diffuse large B-cell lymphoma.33 Given the possible different biologic effect
of each FLC subunit,29 we hypothesized that calculating the CSF KFLC/LFLC ratio might yield additional clinical information also in MS. We found that
a low ratio of KFLC/LFLC in CSF was associated
with conversion from CIS to CDMS when dividing
CIS patients at the median of this ratio. Quantitative
comparisons show that this ratio is mainly driven by
differences in LFLC levels, but also KFLC levels
appear to affect the CSF KFLC/LFLC ratio.
Calculating the ratio of CSF KFLC to LFLC seems
therefore to be superior rather than considering each
subunit alone. To what extent this reflects specific
immunologic mechanisms needs further exploration.
Also the definition of a clinically applicable ratio to
predict disease progression will require validation in
an independent cohort.
No differences in KFLC and LFLC levels were
found between patients with active and non-active
disease at the time of lumbar puncture and their proportions were similar in CIS-CDMS converters and
non-converters. However, the interpretation of these
results is limited due to the small number of patients
in each subgroup.
We did not find any correlation of FLC with clinical
data on disease severity, that is, EDSS at lumbar
puncture and EDSS change during follow-up,
although this has been reported in other studies.34,35
However, this may be explained by the fact that we
investigated primarily patients with CIS and a few
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with early MS. Therefore, our cohort had relatively
low disability at baseline and a small range in clinical
change over time, which may have hampered more
robust correlations and needs to be acknowledged as
a limitation of the study. Therefore, future studies
should also investigate patients with more severe and
progressive disease. The same, that is, no or only a
very small change over time holds true for the MRI
metrics investigated which also made it unlikely to
observe meaningful correlations with FLC variables.
One recent study, also investigating CIS patients,
found significant correlations for KFLC variables
with EDSS considering CIS-MS converters and for
LFLC variables with number of gadolinium positive
lesions on MRI.13 In an earlier study, weak but significant correlations were shown for CSF KFLC levels with Gd-enhanced lesion volume (r = 0.188;
p ⩽ 0.001) and T2 lesion volume (r = 0.164;
p ⩽ 0.001) in MS patients (n = 262).26 However, this
study only included RRMS patients and may therefore not be directly comparable to our investigation.
Altogether, our study extends the current notion of the
diagnostic value of FLC and provides evidence for a
prognostic relevance of CSF KFLC and LFLC in CIS.
CSF FLC could not be related to brain tissue damage
as evidenced by MRI. Further research is needed to
validate FLC as prognostic tool in MS in a multi-centre setting, including more progressive forms of MS
and a longer follow-up time.
Acknowledgements
The Binding Site provided assay reagents (Freelite®)
free of charge, but did not assume any other role in the
conduct of the study. M.M.V. and T.S. contributed
equally to this work.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: M.M.V.
received funding from the Austrian Federal Ministry
of Science, Research and Economics and was trained
within the frame of the PhD Program Molecular
Medicine of the Medical University of Graz. T.S.,
L.P., M.J., C.L., H.S., M.R. and S.R. declare that there
is no conflict of interest. T.S.-H. received speaker
honoraria and support from Teva, Novartis, Biogen
and Eisai. J.-J.A. declares that there is no conflict of
interest. S.F. serves on scientific advisory boards for
Biogen Idec, Novartis, Genzyme, Merck Serono and
TEVA Pharmaceutical Industries and has received
funding for travel and speaker honoraria from Bayer
Schering, Merck Serono, Biogen Idec and
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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017

Contents
Multiple Sclerosis Journal - October 2017 - Cover1
Multiple Sclerosis Journal - October 2017 - Cover2
Multiple Sclerosis Journal - October 2017 - Contents
Multiple Sclerosis Journal - October 2017 - ii
Multiple Sclerosis Journal - October 2017 - iii
Multiple Sclerosis Journal - October 2017 - 1436
Multiple Sclerosis Journal - October 2017 - 1437
Multiple Sclerosis Journal - October 2017 - 1438
Multiple Sclerosis Journal - October 2017 - 1439
Multiple Sclerosis Journal - October 2017 - 1440
Multiple Sclerosis Journal - October 2017 - 1441
Multiple Sclerosis Journal - October 2017 - 1442
Multiple Sclerosis Journal - October 2017 - 1443
Multiple Sclerosis Journal - October 2017 - 1444
Multiple Sclerosis Journal - October 2017 - 1445
Multiple Sclerosis Journal - October 2017 - 1446
Multiple Sclerosis Journal - October 2017 - 1447
Multiple Sclerosis Journal - October 2017 - 1448
Multiple Sclerosis Journal - October 2017 - 1449
Multiple Sclerosis Journal - October 2017 - 1450
Multiple Sclerosis Journal - October 2017 - 1451
Multiple Sclerosis Journal - October 2017 - 1452
Multiple Sclerosis Journal - October 2017 - 1453
Multiple Sclerosis Journal - October 2017 - 1454
Multiple Sclerosis Journal - October 2017 - 1455
Multiple Sclerosis Journal - October 2017 - 1456
Multiple Sclerosis Journal - October 2017 - 1457
Multiple Sclerosis Journal - October 2017 - 1458
Multiple Sclerosis Journal - October 2017 - 1459
Multiple Sclerosis Journal - October 2017 - 1460
Multiple Sclerosis Journal - October 2017 - 1461
Multiple Sclerosis Journal - October 2017 - 1462
Multiple Sclerosis Journal - October 2017 - 1463
Multiple Sclerosis Journal - October 2017 - 1464
Multiple Sclerosis Journal - October 2017 - 1465
Multiple Sclerosis Journal - October 2017 - 1466
Multiple Sclerosis Journal - October 2017 - 1467
Multiple Sclerosis Journal - October 2017 - 1468
Multiple Sclerosis Journal - October 2017 - 1469
Multiple Sclerosis Journal - October 2017 - 1470
Multiple Sclerosis Journal - October 2017 - 1471
Multiple Sclerosis Journal - October 2017 - 1472
Multiple Sclerosis Journal - October 2017 - 1473
Multiple Sclerosis Journal - October 2017 - 1474
Multiple Sclerosis Journal - October 2017 - 1475
Multiple Sclerosis Journal - October 2017 - 1476
Multiple Sclerosis Journal - October 2017 - 1477
Multiple Sclerosis Journal - October 2017 - 1478
Multiple Sclerosis Journal - October 2017 - 1479
Multiple Sclerosis Journal - October 2017 - 1480
Multiple Sclerosis Journal - October 2017 - 1481
Multiple Sclerosis Journal - October 2017 - 1482
Multiple Sclerosis Journal - October 2017 - 1483
Multiple Sclerosis Journal - October 2017 - 1484
Multiple Sclerosis Journal - October 2017 - 1485
Multiple Sclerosis Journal - October 2017 - 1486
Multiple Sclerosis Journal - October 2017 - 1487
Multiple Sclerosis Journal - October 2017 - 1488
Multiple Sclerosis Journal - October 2017 - 1489
Multiple Sclerosis Journal - October 2017 - 1490
Multiple Sclerosis Journal - October 2017 - 1491
Multiple Sclerosis Journal - October 2017 - 1492
Multiple Sclerosis Journal - October 2017 - 1493
Multiple Sclerosis Journal - October 2017 - 1494
Multiple Sclerosis Journal - October 2017 - 1495
Multiple Sclerosis Journal - October 2017 - 1496
Multiple Sclerosis Journal - October 2017 - 1497
Multiple Sclerosis Journal - October 2017 - 1498
Multiple Sclerosis Journal - October 2017 - 1499
Multiple Sclerosis Journal - October 2017 - 1500
Multiple Sclerosis Journal - October 2017 - 1501
Multiple Sclerosis Journal - October 2017 - 1502
Multiple Sclerosis Journal - October 2017 - 1503
Multiple Sclerosis Journal - October 2017 - 1504
Multiple Sclerosis Journal - October 2017 - 1505
Multiple Sclerosis Journal - October 2017 - 1506
Multiple Sclerosis Journal - October 2017 - 1507
Multiple Sclerosis Journal - October 2017 - 1508
Multiple Sclerosis Journal - October 2017 - 1509
Multiple Sclerosis Journal - October 2017 - 1510
Multiple Sclerosis Journal - October 2017 - 1511
Multiple Sclerosis Journal - October 2017 - 1512
Multiple Sclerosis Journal - October 2017 - 1513
Multiple Sclerosis Journal - October 2017 - 1514
Multiple Sclerosis Journal - October 2017 - 1515
Multiple Sclerosis Journal - October 2017 - 1516
Multiple Sclerosis Journal - October 2017 - 1517
Multiple Sclerosis Journal - October 2017 - 1518
Multiple Sclerosis Journal - October 2017 - 1519
Multiple Sclerosis Journal - October 2017 - 1520
Multiple Sclerosis Journal - October 2017 - 1521
Multiple Sclerosis Journal - October 2017 - 1522
Multiple Sclerosis Journal - October 2017 - 1523
Multiple Sclerosis Journal - October 2017 - 1524
Multiple Sclerosis Journal - October 2017 - 1525
Multiple Sclerosis Journal - October 2017 - 1526
Multiple Sclerosis Journal - October 2017 - 1527
Multiple Sclerosis Journal - October 2017 - 1528
Multiple Sclerosis Journal - October 2017 - 1529
Multiple Sclerosis Journal - October 2017 - 1530
Multiple Sclerosis Journal - October 2017 - 1531
Multiple Sclerosis Journal - October 2017 - 1532
Multiple Sclerosis Journal - October 2017 - 1533
Multiple Sclerosis Journal - October 2017 - 1534
Multiple Sclerosis Journal - October 2017 - 1535
Multiple Sclerosis Journal - October 2017 - 1536
Multiple Sclerosis Journal - October 2017 - 1537
Multiple Sclerosis Journal - October 2017 - 1538
Multiple Sclerosis Journal - October 2017 - 1539
Multiple Sclerosis Journal - October 2017 - 1540
Multiple Sclerosis Journal - October 2017 - 1541
Multiple Sclerosis Journal - October 2017 - 1542
Multiple Sclerosis Journal - October 2017 - 1543
Multiple Sclerosis Journal - October 2017 - 1544
Multiple Sclerosis Journal - October 2017 - 1545
Multiple Sclerosis Journal - October 2017 - 1546
Multiple Sclerosis Journal - October 2017 - 1547
Multiple Sclerosis Journal - October 2017 - 1548
Multiple Sclerosis Journal - October 2017 - 1549
Multiple Sclerosis Journal - October 2017 - 1550
Multiple Sclerosis Journal - October 2017 - 1551
Multiple Sclerosis Journal - October 2017 - 1552
Multiple Sclerosis Journal - October 2017 - 1553
Multiple Sclerosis Journal - October 2017 - 1554
Multiple Sclerosis Journal - October 2017 - 1555
Multiple Sclerosis Journal - October 2017 - 1556
Multiple Sclerosis Journal - October 2017 - 1557
Multiple Sclerosis Journal - October 2017 - 1558
Multiple Sclerosis Journal - October 2017 - 1559
Multiple Sclerosis Journal - October 2017 - 1560
Multiple Sclerosis Journal - October 2017 - 1561
Multiple Sclerosis Journal - October 2017 - 1562
Multiple Sclerosis Journal - October 2017 - 1563
Multiple Sclerosis Journal - October 2017 - 1564
Multiple Sclerosis Journal - October 2017 - 1565
Multiple Sclerosis Journal - October 2017 - 1566
Multiple Sclerosis Journal - October 2017 - Cover3
Multiple Sclerosis Journal - October 2017 - Cover4
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