CLB-08261; No. of pages: 5; 4C:
Clinical Biochemistry xxx (2013) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Clinical Biochemistry
journal homepage: www.elsevier.com/locate/clinbiochem
Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser
Diane Maisin ⁎, Thibault Lepoutre, Damien Gruson, Pierre Wallemacq
Department of Clinical Chemistry, Cliniques Universitaires Saint Luc and Université Catholique de Louvain, Brussels, Belgium
a r t i c l e
i n f o
Article history:
Received 16 August 2012
Received in revised form 17 December 2012
Accepted 18 December 2012
Available online xxxx
Keywords:
Free light chains
Immunonephelometry
Immunoturbidimetry
Plasma cell dyscrasias
a b s t r a c t
Objective: Clinical assessment of the SPAPLUS® system for the determination of the serum free light
chains kappa (κ FLC) and lambda (λ FLC) compared to the BNII®.
Design and methods: 126 serum specimens from our routine activity were analysed on two different
analysers: the BNII® (immunonephelometry, Siemens) and the SPAPLUS® (turbidimetry, Binding Site). We
compared the absolute values of the serum κ FLC and λ FLC, as well as the FLC κ/λ ratio on both analysers.
These results were further evaluated together with the clinical history of the patients.
Results: Regression analysis between the BNII® and the SPAPLUS® for κ FLC and λ FLC did not display any
significant differences between both methods in the normal and pathological ranges. Nevertheless, some
differences have been observed for some patients in the absolute value of the involved light chain, with
potential clinical implications.
Conclusion: The results show overall good concordance between both methods. However, it is recommended
that the monitoring of patients affected by monoclonal gammapathies by measuring FLC, be performed in the
same laboratory and by the same method. Moreover, the FLC results should always be interpreted together
with other laboratory tests taking into account the patient's diagnosis.
© 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction
Materials and methods
A serum free light chain (FLC) assay has a number of indications in
the evaluation and management of multiple myeloma (MM) and
plasma cell dyscrasias (PCD). It plays a major role in the screening
and diagnosis of PCD, and in the prognosis of nearly all PCD [1,2].
The FLC assay allows also quantitative monitoring of patients with
light chain myeloma, oligosecretory myeloma and light chain amyloidosis [2–5].
The immunoassay for serum free light chain (Freelite, The Binding
Site, Birmingham, UK), is based on a commercial reagent set of polyclonal antibodies coated onto polystyrene latex [6].
These antibodies react with the epitopes on the serum light chains
that were hidden when bound to heavy chains, but available in case
of dissociation. These reagents are adapted on many nephelometric
and turbidimetric laboratory platforms. In the context of continuous
consolidation in central laboratories, it appeared relevant to evaluate
the possible move from a nephelometric to a turbidimetric assay, without affecting the analytical performances and the medical interpretation.
We have therefore evaluated in our routine clinical practice the performances of the SPAPLUS ® analyser, based on turbidimetry, in comparison
with our current immunonephelometric method (BNII instrument).
Samples
⁎ Corresponding author at: Department of Clinical Chemistry, Cliniques Universitaires
Saint Luc, 10 Hippocrate Ave., B-1200 Brussels, Belgium. Fax: +32 2 7646930.
E-mail address: [email protected] (D. Maisin).
126 serum specimen from our routine activity were measured on
the BNII® instrument (Siemens Healthcare Diagnostics, Deerfield,
IL, USA), stored frozen (at − 20 °C) until the determination on the
SPAPLUS® analyser (The Binding Site, Birmingham, UK). Most patients were followed at the Cliniques Universitaires St. Luc, Brussels,
Belgium, for various haematological disorders such as multiple
myeloma (n: 78 MM including 44 light chain myeloma, LCMM),
amyloidosis (n: 1 AL), chronic lymphocytic leukaemia (n: 1 CLL),
lymphoma (n: 2), Plasmocytoma (n: 4), polycythemia vera (n: 1)
or monoclonal gammapathies of undetermined significance (n: 12
MGUS). However, serum samples from patients followed in other centres,
with unknown, diagnosis (n: 9 external patients EP) or serum samples
from non-PCD patients (n: 18 screening patients) were also collected
and analysed. The study was in agreement with our local ethics committee. Serum and control specimens were analysed according to the
manufacturer's instructions.
For the BNII® the working dilution is 1/100 and allows a quantification range of 5.9–190 mg/L and 5–160 mg/L, for the serum κ FLC
and serum λ FLC, respectively; sensitivity at the dilution of 1/5 is
0.3 mg/L and 0.25 mg/L for the serum κ and λ FLC, respectively.
If the dilution 1/100 is inadequate and the FLC is above the upper
limit of the measuring range or below the lower limit, the BNII® starts
automatically other dilutions ranging from 1/1 up to 1/8000.
0009-9120/$ – see front matter © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015
Please cite this article as: Maisin D, et al, Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser, Clin Biochem
(2013), http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015
2
D. Maisin et al. / Clinical Biochemistry xxx (2013) xxx–xxx
For the SPAPLUS® the working dilution is 1/10 and allows a quantification ranging from 4–180 mg/L and 4.5–165 mg/L for the serum
κ and λ FLC, respectively; sensitivity at 1/1 is 0.4 mg/L and 0.5 mg/L
for the serum κ FLC and serum λ FLC, respectively.
If the dilution 1/10 is inadequate, the SPAPLUS® starts automatically
other dilutions, either 1/1 or 1/100. All other dilutions have to be done
manually.
The normal ranges were defined by Katzmann et al. with the 95%
reference interval for κ FLC ranging from 3.3–19.4 mg/L and that for λ
FLC was 5.7–26.3 mg/L [7].
The 100% reference interval for the FLC κ/λ ratio was 0.26–1.65.
Patients with a ratio > 1.65 are characterised by an excess of κ FLC,
and patients with a ratio b0.26 have an excess of λ FLC. Those patients
are most likely producing clonal light chains.
An abnormal FLC κ/λ ratio was considered discordant if b 0.26 for a
κ disease, and >1.65 for a λ disease.
The analyses were performed on both automates, with different
reagents lots, since the FLC kits are prepared specifically for each
instrument.
We measured total immunoglobulins A, M and G by
immunonephelometry on the BNII®. Serum protein electrophoresis
(SPE) was performed by capillary electrophoresis (Capillarys 2R, Sebia,
Issy-les-Moulineaux France). Urine and serum immunofixation (IF)
were performed by gel electrophoresis (Semi-automated Hydrasys,
Sebia, Issy-les-Moulineaux France).
The inter-day imprecision data for both instruments were
obtained by repeating quality control levels (levels 1 and 2) for κ
(in the ranges of 16 and 30 mg/L) and λ (in the ranges of 28 and
55 mg/L) during 12 consecutive days.
Statistical analysis
Statistical analysis was performed using MedCalc (Medcalc Software,
Mariakerke, Belgium). Evaluation of normality was performed with the
Kolmogorov–Smirnov test. Passing and Bablok regression analyses and
Bland and Altman plots were used for method comparison. A p-value
≤0.05 was considered significant.
Results
The inter-day imprecision values for the BNII were 9.7% (level 1)
and 5.6% (level 2), and 7.5% (level 1) and 5.7% (level 2), respectively
for κ and λ light chains.
The inter-day imprecision values for the SPAPLUS® were 9.3%
(level 1) and 12.1% (level 2), and 10.9% (level 1) and 5.1% (level 2),
respectively for κ and λ light chains.
In the low and normal ranges ≤ 19.4 mg/L for κ FLC and ≤ 26.3 for
λ FLC, mean BNII® concentrations for κ FLC, and λ FLC were 9.77 and
12.25 mg/L, respectively; and on the SPAPLUS®, 9.93 and 10.03 mg/L,
respectively. Regression analyses between the 2 methods showed
for κ FLC, and λ FLC slopes of 1.095 (95% CI: 0.958 to 1.278) and
0.912 (95% CI: 0.864 to 0.970), and intercepts of − 1.182 (− 3.023
to 0.143) and − 0.760 (95% CI: − 1.490 to − 0.188) respectively
(Fig. 1A, B). Bland and Altman plots revealed mean differences of −
0.2 mg/L for κ FLC and 2.2 mg/L for λ FLC.
In the higher ranges of values >19.4 mg/L for κ FLC and >26.3 mg/L
for λ FLC, mean concentrations for κ FLC, and λ FLC were respectively
998 mg/L and 1288 mg/L on the BNII®, and 876 and 1477 mg/L for
the SPAPLUS®. Regression analysis between the 2 methods displayed
for κ FLC and λ FLC slopes of 0.899 (95% CI: 0.838 to 0.982) and 1.060
(95% CI: 0.987 to 1.262) and intercepts of 1.188 (95% CI: − 2.617 to
4.018) and − 7.030 (95% CI: − 16.444 to − 3.717), respectively
(Fig. 2A, B). Bland and Altman plots revealed mean differences of
122 mg/L for κ FLC and − 189 mg/L for λ FLC.
The lower and upper FLC concentrations were 0.1 to 10,800 mg/L
and 0.5 to 22,300 respectively for κ FLC and λ FLC for BNII®.
The lower and upper FLC concentrations were 0.36 to 11,004 mg/L
and 0.9 to 22,818 respectively for κ FLC and λ FLC for SPAPLUS®.
Concerning the involved FLC, it seems that the BNII® produces
higher values than the SPAPLUS® for κ FLC values >1500 mg/L, and
lower values for λ FLC values >1000 mg/L as displayed by Fig. 2.
If we focus on the value of κ FLC and λ FLC around 600 mg/L, the difference between both methods seems generally minor (Fig. 3A and B).
For higher values, for a few samples, discrepancies between methods
spread up to 2264 mg/L for κ FLC and up to 5018 mg/L for λ FLC.
To evaluate if those differences could lead to different clinical interpretation, we analysed the follow up of 13 patients with a minimum of
two different values of light chains measured at different intervals
(maximum 3 month follow up).
Eight patients (data not shown) have similar absolute values of
the involved light chain and display identical evolution with the time.
Four patients (data not shown) have different absolute values
(>20%) of the involved light chain, but even if the general evolution
with time appears similar in both methods, the magnitude of these variations is not identical, and remains lot- and or instrument-dependent,
as illustrated for patient #12 suffering from κ light chain myeloma in
Table 1.
One patient was totally discordant (patient #13), presenting
an increased value with time for the involved light chain on
SPAPLUS® and a constant decreased value on BNII®, as shown in
Table 2. This discordance has been reduced when repeated with
B
25
SPAPLUS® λ FLC (mg/L)
SPAPLUS® κ FLC (mg/L)
A
Measurement of kappa and lambda free light chains
20
15
10
5
0
30
25
20
15
10
5
0
0
5
10
15
BNII® κ FLC (mg/L)
20
25
0
5
10
15
20
25
30
BNII® λ FLC (mg/L)
Fig. 1. Regression analysis between BNII® and SPAPLUS® analysers for κ FLC (n: 62) (A) and λ FLC (n: 83) (B) for low and normal values. The 95% confidence interval is illustrated by
the dotted lines, together with the identity and regression lines.
Please cite this article as: Maisin D, et al, Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser, Clin Biochem
(2013), http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015
D. Maisin et al. / Clinical Biochemistry xxx (2013) xxx–xxx
B
12000
SPAPLUS® λ FLC (mg/L)
SPAPLUS® κ FLC (mg/L)
A
10000
8000
6000
4000
2000
3
25000
20000
15000
10000
5000
0
0
0
4000
8000
12000
0
5000
BNII® κ FLC (mg/L)
10000 15000 20000 25000
BNII® λ FLC (mg/L)
Fig. 2. Regression analysis between BNII® and SPAPLUS® analysers for κ FLC (n: 64) (A) and λ FLC (n: 43) (B) for abnormal values. The 95% confidence interval is illustrated by the
dotted lines, together with the identity and regression lines.
another BNII reagent lot. It should be noted that the first sample
was slightly haemolysed.
Calculation of the serum FLC κ/λ ratio
Mean values for FLC κ/λ in the ranges b 0.26; between 0.26 and
1.65 and > 1.65 were 0.070, 0.849, and 283.4 for the BNII®, and
0.076, 1.058 and 382.6 for the SPAPLUS®, respectively. Regression
analysis for FLC κ/λ between the 2 methods in the ranges b0.26;
between 0.26 and 1.65 and > 1.65 showed slopes of 1.0 (95% CI:
0.845 to 1.274), 1.2 (95% CI: 0.990 to 1.481) 1.129 (95% CI: 1.023 to
1.332) and intercepts of 0.00 (95% CI: − 0.000 to 0.002), − 0.064
(95% CI: − 0.270 to 0.087), and 0.106 (95% CI: − 1.003 to 1.323),
respectively. Bland and Altman plots revealed mean differences
of − 0.006, − 0.2 and − 99.2, for ranges b 0.26; between 0.26 and
1.65 and > 1.65, respectively.
Despite the fact that the regression analysis between the
BNII® and the SPAPLUS® showed no significant deviation from linearity for the normal and the pathological values, we observed
8 individual differences in the κ/λ ratio between both methods.
4 samples (patients #14 #15b #17 #20) had a normal κ/λ ratio for the
BNII®, but slightly elevated for SPAPLUS®. One sample (patient #16)
had a normal κ/λ ratio for the SPAPLUS® and slightly elevated for
BNII®. One sample (patient #18) had a normal κ/λ ratio for the
SPAPLUS®, slightly reduced for BNII®. Two samples (patients #15
and #19) have a κ/λ ratio discordant on SPAPLUS® either increased
in the context of a λ disease or decreased in the context of κ disease (Table 3, Fig. 4).
FLC has shown clinical utility as a complementary test to serum
protein electrophoresis (SPE), immunofixation (IFE) of serum and
urine, for diagnosis, prognosis and monitoring of PCD. A large number
of publications report difficulties in measuring κ and λ free light
chains [8–10]. Between-lot imprecision in the assay has been reported
ranging from 8 to 45% [9] with a significant effect on the calculated
FLC κ/λ ratio. Some monoclonal light chains do not display linearity in
the dilution and the value may be underestimated in the absence of
additional dilution [9]. Some other monoclonal light chains may fail to
react with different lots of reagent [11]. In this study, we have compared
results obtained on the BNII® and the SPAPLUS® analysers from 126
routine samples. Discrepancies were further analysed with the clinical
status of the patient to evaluate the clinical impact.
We first compared the absolute values of both free light chains κ
and λ obtained on both instruments. As reported previously [4] for
monitoring patients with light chain myeloma, oligosecretory myeloma and light chain amyloidosis, the involved FLC has to be considered. Despite the fact that, regression analysis between the BNII®
and the SPAPLUS® showed no significant deviations from linearity
for the normal and the pathological values, illustrating no important
bias between both methods, we observed for some patients significant differences in the absolute value of κ and λ.
As described above, we could partly explain those differences by
the different lots of antisera between both methods. (Kits may not
be commutable). Other possible explanations could be related to
the different technologies involved (immunonephelometry versus
B
700
600
SPAPLUS® λ FLC (mg/L)
SPAPLUS® κ FLC (mg/L)
A
Discussion
600
500
400
300
200
100
500
400
300
200
100
0
0
0
200
400
BNII® κ FLC (mg/L)
600
0
100
200
300
400
500
600
BNII® λ FLC (mg/L)
Fig. 3. Regression analysis between BNII® and SPAPLUS® analysers for κ FLC (A) and λ FLC (B) up to 600 mg/L. The 95% confidence interval is illustrated by the dotted lines, together
with the identity and regression lines.
Please cite this article as: Maisin D, et al, Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser, Clin Biochem
(2013), http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015
4
D. Maisin et al. / Clinical Biochemistry xxx (2013) xxx–xxx
Table 1
Time-evolution profile for patient #12 with κ light chain myeloma on both instruments,
illustrating differences in absolute κ FLC values but with a similar trend over time.
Date
Spa κ (mg/L)
BNII κ (mg/L)
7/12/2010
17/1/2011
27/1/2011
12/2/2011
1173
811
908
619
853
614
851
446
Table 2
Monitoring of patient #13 with a κ light chain myeloma on SPAPLUS® and on BNII®
with two different reagent lots (lot 130953BS and lot 130959BS). Instrument dilutions
are indicated inside parentheses.
Date
Spa κ (mg/L)
BNII κ (mg/L)
Lot 130553BS
BNII κ (mg/L)
Lot 130959BS
24/1/2011
9/2/2011
10/2/2011
19/3/2011
116 (1/10)
288 (1/100)
301 (1/100)
347 (1/400)
128 (1/100)
133 (1/100)
64 (1/100)
456
305
281
333
(1/400)
(1/400)
(1/400)
(1/400)
immunoturbidimetry), different dilutions used, and possibly different analytical protocols (e.g. incubation times).
The recommended reference ranges appear identical on both
analysers, suggesting an absence of any significant differences at
least in the normal ranges. However, we demonstrated significant
differences in case of higher FLC concentrations.
These differences in the absolute value of the involved light chain
could lead to difficulties in the monitoring of PCD in case of switching
the technique during a patient follow-up (Table 1).
Clinical criteria for multiple myeloma treatment response, such as
“very good partial response, partial response or stable disease” [12]
should require measurement of free light chains in the same laboratory,
with the same method. If the antisera lot changed, as recommended by
Tate et al., the previous stored sample should ideally be re-run using the
new batch together with the new sample [11].
One patient (#13) was totally discordant, presenting an increased
value for the involved light chain on SPAPLUS® and a constant decreased value on BNII®, as shown in Table 2. This discordance has
been reduced when repeated with another BNII reagent lot. As a
reminder, all samples are processed with automated dilution. The
values >50 mg/L for κ FLC and >100 mg/L for λ FLC [9] were not systematically reanalysed (following the manufacturer's instructions).
The discordance observed in Table 2 could be explained by a problem
of non linearity of monoclonal free light chain occurring for some
samples on both instruments [9].
Concerning the κ/λ ratio, despite the fact that the regression analysis
between the BNII® and the SPAPLUS® showed no significant deviation
from linearity for the normal and the pathological values, we observed
a few individual differences in the κ/λ ratio, that can be explained by
differences in the absolute values of κ and λ as describe above.
Abnormal concentrations of κ and λ FLC may reflect numbers of clinical situations including reduced renal clearance, immunosuppression
or -stimulation, and monoclonal plasma cell proliferative disorders.
Sera from patients with either polyclonal hypergammaglobulinemia
or renal impairment often display elevated κ FLC and λ FLC due to
increased synthesis or reduced renal clearance. In these conditions, borderline increased FLC κ/λ can occur [13]. For renal impairment, to avoid
false positive, FLC κ/λ ratio reference ranges are modified to 0.37–3.17
[14] instead of the standard ratio reference range (0.26–1.65).
Patient #20 (κ LCMM; post autograft, post treatment with
thalidomide) presents an unclear elevation of both κ and λ FLC,
with a FLC κ/λ ratio normal on BNII® and slightly increased on
SPAPLUS®.
A significant abnormal FLC κ/λ ratio should only be due to a plasma
proliferative disorder that secretes excess FLC and disturbs the normal
balance between κ and λ secretion. But at very low concentrations the
precision of the measurement is poor, and the accuracy of the FLC κ/λ
has to be reconsidered [4,9], as shown in patient #14, the measurement
has been repeated on the SPAPLUS® the same day with FLC κ/λ ratio
normalisation.
Similarly, patient #17 (IgA κ MGUS) has κ and λ FLC in the normal
ranges on both analysers, but with a FLC κ/λ ratio slightly abnormal
for SPAPLUS®. Patient #19 (λ LCMM and renal insufficiency) presents
κ FLC increase on SPA® in the context of a λ disease.
Recently, it has been published that oligoclonal bands, (suggesting
a robust humoral immune response to therapy) could result in an abnormal FLC κ/λ ratio [15]. Furthermore, in the case of patients with
bone marrow suppression, the alternate FLC may have low concentration and patients who have undergone autologous stem cell transplantation for light chain myeloma could have discordant FLC κ/λ
ratio [9]. This could be illustrated by patient #15, presenting a κ
LCMM, post autograft and in complete remission. In the patient history
the FLC κ/λ ratio appears sometimes in the normal, lower or upper
ranges. Any calculated ratios at these levels of FLC is of uncertain
significance.
That should be kept in mind as the FLC κ/λ can be used to identify
stringent complete response in MM [15,16].
Following the manufacturer's instructions, the control results
should only be accepted if the results obtained are within 20% of
Table 3
Differences in the κ/λ ratio between both methods together with clinical diagnosis if available.
Patient #
Diagnosis
Spa κ (mg/L)
BNII κ (mg/L
Spa λ (mg/L)
BNII λ (mg/L)
Spa κ/λ
BNII κ/λ
SPE
Serum
IF
Urine
IF
14
14a
15
15b
16
17
18
19
20
IgG κ myeloma
IgG κ myeloma
κ LCMMc
κ LCMM
CLL with RI
IgA κ MGUS
External patient
λ LCMM with RI
κ LCMMd
12.7
10.3
0.6
8.1
25.4
17.6
22.3
30.1
69
10.6
10.6
6.1
5.6
39.1
16.3
18.4
19.7
52.4
7
6.6
5.3
1.7
15.4
8.8
78.1
16.2
39.1
8.1
8.1
2.8
7.8
19.6
11.4
84.2
18.5
43.5
1.8
1.57
0.11
4.89
1.65
2
0.28
1.86
1.77
1.31
1.31
2.18
0.72
1.99
1.43
0.22
1.06
1.20
+
+
–
–
–
+
+
+
–
–
–
+
+
+
–
–
+
+
–
–
–
–
–
–
Reference range κ FLC: 3.3–19.4 mg/L; reference range λ FLC: 5.7–26.3 mg/L; diagnosis range FLC κ/λ ratio: 0.26–1.65.
RI: renal insufficiency.
a
Rerun the same day on SPA.
b
Same patient but new sample two months later.
c
Post autograft and in CR (complete remission).
d
Post autograft, post treatment with thalidomide.
Please cite this article as: Maisin D, et al, Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser, Clin Biochem
(2013), http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015
D. Maisin et al. / Clinical Biochemistry xxx (2013) xxx–xxx
concentrations of FLC is not indicated for disease monitoring due to
its important variability [8,9,17].
It is important to remember that for κ and λ FLC measurements,
samples need to be measured with the same technology in the same
laboratory. Even following such recommendations, there are still variations from lot to lot that can occur on different instruments even on the
SPAPLUS®. For all instruments the problem of non linearity and antigen
excess can occur, justifying ideally systematic reanalysis at different
dilutions if financially and practically acceptable.
SPAPLUS® FLC κ/λ ratio
10
8
6
15b
4
20
14
17
19
References
2
16
18
15
0
0
5
1
2
3
4
5
BNII® FLC κ/λ ratio
Fig. 4. Regression analysis FLC κ/λ ratios obtained from BNII® and SPAPLUS® analysers
in the low and slightly elevated values. Discrepant values are illustrated as black boxes
together with the corresponding patient reference number, as appearing in Table 3.
the concentrations stated. This suggests a poor precision of the assay
at low and normal ranges, questioning the interest to provide one
decimal to the results as recommended by the manufacturer.
It has to be kept in mind that the FLC κ/λ ratio has to be
interpreted in association with other clinical laboratory tests such as
serum electrophoresis, immunofixation, urine analysis, and with the
clinical history of the patient.
If we interpret the results of these 8 samples (from 7 patients)
with their clinical history, none of these discrepancies between the
two methods appears to be clinically significant.
Conclusion
In light of these results we can conclude that it is still difficult to
monitor PCD by measuring FLC. In our study we have compared results between two routine analysers, based on different technologies
and also involving different reagent lots at the dilution recommended
by the manufacturers. When the results were interpreted together
with the clinical status and with other routine tests such as SPE or
urine and serum IF (with the exception of 1 patient characterised
most likely by a problem of non linearity on both instruments), we
didn't observe any significant differences between the BNII® and
the SPAPLUS® in the diagnosis and screening. On the other hand, we
observed differences in the absolute values of the involved light
chains mainly at high concentrations. These differences, could lead
to misinterpretation in the monitoring of a disease. We didn't observe
problems of antigen excess in our cohort of 126 samples. Regarding
the FLC κ/λ ratio, the calculation of the ratio at very low or normal
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Please cite this article as: Maisin D, et al, Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser, Clin Biochem
(2013), http://dx.doi.org/10.1016/j.clinbiochem.2012.12.015