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
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Original Article

Volume 9, Number 1, January 2017, pages 46-57

Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio


Table 1. Frequency Distribution of Various Type of Monoclonal Immunoglobulins
Immunoglobulin typeNumber of observationsNumber of patients
IgG K923173
IgG L54397
IgA K30548
IgA L18035
IgM K8833
IgM L3714
IgD K101
IgD L262
Kappa only19340
Lambda only8822
Total kappa (including non-secretory)1,535
Total lambda874


Table 2. Performance of Electrophoretic Methods and SFLCA κ/λ Ratio With Respect to Level of Concordance With the Established Diagnosis of Monoclonal Gammopathy
The total 2,409 observations were graded for concordance with the established diagnoses. The results of the electrophoretic methods had significantly higher concordance with the established diagnoses, P < 0.00001. The results of the electrophoretic method had significantly lower discordance rate with a P < 0.00001.
P << 0.00001


Table 3. The Concordance Rates of the Two Methods for Light Chain Specific Results
Concordance levelKappa (N = 1,535) (including non-secretory)Lambda (N = 874)
Electrophoretic methods had significantly higher concordance with the established diagnoses for both kappa and lambda light chain monoclonal gammopathies than serum free light chain κ/λ ratio assay results.
P < 0.00001 (X2 = 26.1)P << 0.00001 (X2 = 344.2)


Table 4. The Samples in Which a Monoclonal Ig Was Detectable by Electrophoretic Methods Were Identified and the False Negative Rate for SFLCA κ/λ Ratio for the Grand Total, Kappa Chain Lesions, Lambda Chain Lesions and Clinical Diagnoses of MGUS, SMM and MM Are Provided
Number of observationsElectrophoretic positive, NK/L ratio negative, NFalse negative rate for K/L, %
The greater than 55% false negative rate for κ/λ ratio for MGUS patients is noteworthy and argues against a role of SFLCA as a screening tool for monoclonal gammopathy.
Grand total2,4091,86050126.94
Kappa chain lesions1,5351,14227123.73
Lambda chain lesions87472223031.86


Table 5. Comparative Results of SFLCA and Electrophoretic Methods at the First Encounter With a Given Patient Are Given Below
Serum free light chain assay at first encounter with a given patient
Kappa chain lesionsLambda chain lesionsFalse Neg, %
The false negative κ/λ ratio results are particularly noteworthy in treatment naive MGUS patients at a rate of 67%. The high false negative rate for lesions with lambda light chains, nearly 90%, is in keeping with the high false negative rate for lambda light chain lesions in other settings.
  K/L ratio +323
  K/L ratio -4724
  Kappa chain lesions59.49
  Lambda chain lesions88.89
  K/L ratio +82
  K/L ratio -03
  Kappa chain lesions0
  Lambda chain lesions60
  K/L ratio +13944
  K/L ratio -3346
  Kappa chain lesions19.19
  Lambda chain lesions51.11


Table 6. Poor Performance of SFLCA κ/λ Ratio in a Patient With IgG Lambda Myeloma
Time of assaySPEP spike, g/dLIg typeKappaLambdaκ/λ ratio
The entries in this table display an example of the poor performance of SFLCA and κ/λ ratio in patients with lambda light chain monoclonal gammopathies. In this case, the SFLCA and κ/λ ratios were consistently negative and discordant despite the fact that each of the 25 samples had a readily detectable monoclonal IgG lambda monoclonal protein. The serum creatinine in this patient was 1.06 mg/dL and renal κ/λ ratio would not have been applicable.
April 20131.69IgG L13.2417.970.74
December 20121.49IgG L17.7312.771.39
August 20121.44IgG L2.594.010.65
June 20121.07IgG L3.864.170.93
December 20111.1IgG L2.243.850.58
August 20111.32IgG L2.783.590.77
May 20111.07IgG L1.673.510.48
April 20110.89IgG L2.375.680.42
March 20110.95IgG L1.563.330.47
January 20110.97IgG L1.042.710.38
November 20100.82IgG L1.592.680.59
August 20100.66IgG L1.011.380.73
June 20100.74IgG L1.62.560.63
May 20101.19IgG L1.765.110.34
April 20101.2IgG L1.823.880.47
February 20101.17IgG L1.723.890.44
December 20091.34IgG L1.982.110.94
October 20091.18IgG L1.92.210.86
September 20091.38IgG L2.272.261.00
August 20091.34IgG L1.552.590.60
June 20090.77IgG L2.032.460.83
May 20090.8IgG L2.911.51.94
March 20090.9IgG L1.951.611.21
January 20090.7IgG L2.361.641.44
November 20080.7IgG L2.331.651.41


Table 7. The Performance of the Two Methods, i.e., Electrophoretic Methods and SFLCA, for Plasma Cell Myeloma (MM), Smoldering Multiple Myeloma (SMM) and Monoclonal Gammopathy of Undetermined Significance (MGUS) Are Presented
CategoryNumberMethodConcordance level for observations onlyP value (total concordance)
The concordance of the electrophoretic method results with the established diagnosis was superior to the results of SFLCA in all of the three categories of patients. The level of discordance with the established diagnosis was significantly lower with electrophoretic results than for SFLCA in patients with MM and MGUS. There were insufficient observations in the SMM group for comparison of discordance levels. There was one discordant result, each, with both methods.
  Observations1,831SFLC1,06671154< 0.00001
  Observations295SFLC13214815< 0.00001


Table 8. Comparison of the Electrophoretic and SFLCA Results in Samples in Which the Results of the Two Method Were Not in Agreement With Each Other
Test methodTotalKappaLambda
Concordant, NConcordant, %Concordant, NConcordant, %Concordant, NConcordant, %
The finding of superiority of the electrophoretic method was applicable in monoclonal gammopathies with both kappa and lambda light chains. As is apparent from the numbers and percentages, the results for lambda light monoclonal gammopathies were far better for electrophoretic methods than for SFLCA κ/λ ratio.
SFLCA κ/λ ratio21022.2617336.34377.92
P < 0.00001P < 0.00001P << 0.00001 (X2 = 695.5)