Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website http://www.jocmr.org

Original Article

Volume 10, Number 7, July 2018, pages 562-569

Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies

Figure

Figure 1.
Figure 1. SIFE and UIFE results for the instructive patient with biclonal gammopathy. The results from this patient with biclonal gammopathy are instructive. The lack of lambda dominant κ/λ ratio and absence of monoclonal lambda chains in urine strongly suggest underproduction of excess free lambda light chains. We estimate that out of the total 30% false negative rate for lambda dominant κ/λ ratio, by the SFLCA, about 5% are due to under-production of excess free lambda light chains and about 25% due to under-detection of monoclonal lambda light chains by the Binding Site assay, or due to excess production of polyclonal kappa light chains in tertiary care patients thus resulting in distorted κ/λ ratio in patients with lambda chain lesions.

Tables

Table 1. Distribution of SFLCA Results of Patients With Monoclonal Gammopathies Categorized by UIFEs
 
Total Pool of monoclonal gammopathiesStatistics
KappaLambda
This table includes 193 patients with 279 observations, in the presence of monoclonal immunoglobulin in serum, SPEP/SIFE, UPEP/UIFE, SFLCA and light chain type of the primary lesion were available. In the total pool as well as the three subgroups of UIFE 0, (no monoclonal immunoglobulin detected in urine) UIFE 1 (monoclonal light chains, with or without intact immunoglobulins) in urine, and UIFE 2 (intact monoclonal immunoglobulin detected in urine), kappa chain lesions displayed kappa dominant κ/λ ratio in serum, significantly more often than observed with lambda dominant κ/λ ratio in lesions with lambda light chains. The findings, along with data shown later, imply systematic under-detection of lambda light chains by the Binding Site assay, or the alternative explanation of over production of polyclonal kappa light chains. The P values correspond to the χ2 calculations showing the difference in the SFLCA results for kappa vs. lambda chain lesions. Neg.: κ/λ ratio was not dominant for the relevant light chain; Pos.: κ/λ ratio was dominant for the relevant light chain.
Neg.Pos.Neg.Pos.
UIFE 02430287χ2 = 11.05, P = 0.00089
UIFE 15781545χ2 = 10.42, P = 0.0012
UIFE 2527105χ2 = 12.24, P = 0.00047
Total341355357χ2 = 24.45, P < 0.00001

 

Table 2. Relative Distribution of the Neoplastic Monoclonal Gammopathies With Respect to the Categories of UIFE
 
MGUSMMSMM
Total of 249 observations of neoplastic monoclonal gammopathies are included.
UIFE024522
UIFE1181017
UIFE272810

 

Table 3. Distribution of SFLCA Results of Patients With Neoplastic Monoclonal Gammopathies Categorized by UIFEs
 
StatisticsKappaLambda
Neg.Pos.Neg.Pos.
Relative distribution of various primary lesions of monoclonal gammopathy by UIFE findings, light chain type of the lesion and SFLCA results. Despite small numbers, the results show significantly lower detection rate for lambda dominant κ/λ ratio, in almost all categories. *The category of UIFE 2 for MGUS does not have a statistically significant result, in part, due to the need to substitute 1 for 0 as well as the small number of observations. The P values correspond to the χ2 calculations showing the difference in the SFLCA results for kappa vs. lambda chains. Neg.: κ/λ ratio was not dominant for the relevant light chain; Pos.: κ/λ ratio was dominant for the relevant light chain.
UIFE 0
  MGUSχ2 = 8.71, P = 0.003248111
  MM + SMMχ2 = 4.84, P = 0.0281916163
UIFE 1
  MGUSχ2 = 6.11, P = 0.01301053
  MM + SMMχ2 = 6.70, P = 0.0096065637
UIFE 2
  MGUSχ2 = 1.74, P = 0.18*1420
  MM + SMMχ2 = 7.36, P = 0.006742275

 

Table 4. Distribution of the Light Chain Type of Lesions of Neoplastic Monoclonal Gammopathies With Respect to their UIFE Categories
 
UIFE 0UIFE 1UIFE 2Statistics
The finding of UIFE did not show statistical difference between kappa and lambda chain lesions for the 249 observations of neoplastic monoclonal gammopathies.
Kappa477531χ2 = 1.295 P = 0.52
Lambda315114

 

Table 5. Distribution of SFLCA Results of Patients With Neoplastic Monoclonal Gammopathies (MM + SMM + MGUS) Categorized by UIFEs
 
MM + SMM + MGUS observations
κ/λ ratioStatistics
Neg.Pos.
Categorization of findings in samples with neoplastic monoclonal gammopathies, by UIFE results and kappa vs. lambda light chain type and κ/λ ratio reveal significantly greater prevalence of kappa dominant κ/λ ratio in kappa chain lesions, compared to lambda chain lesions, supporting the notion of systematic under-detection of lambda light chains by the Binding Site assay, or general excess production of polyclonal kappa light chains in tertiary care patients. The P values correspond to the χ2 calculations for the difference in the SFLCA results for kappa vs. lambda chains. Neg.: κ/λ ratio was not dominant for the relevant light chain; Pos.: κ/λ ratio was dominant for the relevant light chain.
UIFE 0K2324χ2 = 11.82
L274P = 0.00059
UIFE 1K075χ2 = 12.91
L1041P = 0.00033
UIFE 2K526χ2 =10.44
L95P = 0.00124

 

Table 6. Distribution of Patients With Neoplastic Monoclonal Gammopathies With SFLCA Results, for UIFE 1 Only
 
Neoplastic monoclonal gammopathy patients
κ/λ ratioStatistics
Neg.Pos.
Results of patients (observations shown in Table 5 for samples) with detectable monoclonal light chains in urine revealed that about 25% of patients have under-detection of lambda dominant κ/λ ratio. The P value by Fischer’s exact test was 0.0001. The P values correspond to the χ2 calculations showing the difference in the SFLCA results for kappa vs. lambda chains. Neg.: κ/λ ratio was not dominant for the relevant light chain; Pos.: κ/λ ratio was dominant for the relevant light chain.
UIFE 1K054χ2 = 11.79
L1031P = 0.0006