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

Abstract

BackgroundSerum free light chain assay (SFLCA) and κ/λ ratio, and protein electrophoretic methods are used in the diagnosis and monitoring of monoclonal gammopathies.MethodsResults for serum free light chains, serum and urine protein electrophoreses and immunofixation electrophoreses in 468 patients with a diagnosis of monoclonal gammopathy were compared. The results of the two methods were graded as concordant, non-concordant or discordant with the established diagnoses to assess the relative performance of the methods. Results of κ/λ ratio in samples with monoclonal protein detectable by electrophoretic methods were also analyzed.ResultsProtein electrophoreses results were concordant with the established diagnoses significantly more often than κ/λ ratio. The false negative rate for κ/λ ratio was higher than that for electrophoretic methods. κ/λ ratio was falsely negative in about 27% of the 1,860 samples with detectable monoclonal immunoglobulin. The false negative rate was higher in lesions with lambda chains (32%) than those with kappa chains (24%). The false negative rate for κ/λ ratio was over 55% in samples with monoclonal gammopathy of undetermined significance. Even at first encounter, the false negative rates for κ/λ ratios for monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma were 66.98%, 23.08%, and 30.15%, respectively, with false negative rate for lambda chain lesions being higher.ConclusionsElectrophoretic studies of serum and urine are superior to SFLCA and κ/λ ratio. Abnormal κ/λ ratio, per se, is not diagnostic of monoclonal gammopathy. A normal κ/λ ratio does not exclude monoclonal gammopathy. False negative rates for lesions with lambda chain are higher than those for lesions with kappa chains. Electrophoretic studies of urine are underutilized. Clinical usefulness and medical necessity of SFLCA and κ/λ ratio is of questionable value in routine clinical testing.

Comparison of Serum Immunoglobulin Free Light Chains Assay and Serum Immunofixation Electrophoresis in Patient Transplanted for Multiple Myeloma

“…Of the 360 samples analyzed, 201 samples (55.8%) had an abnormal κ/λ ratio and 118 samples (32.7%) had an abnormal sIFE appearance (presence of a monoclonal band). Of these 360 samples, 221 had agreement between sIFE and κ/λ ratio and 139 were discordant, with a statistically significant difference in favor of the κ/λ ratio (p <0.0001), which in agreement with what was reported by Milani, et al [22] but discordant with what reported by other authors [14,16,23].…”

“…The mean value of κ/λ in the group which was positive for monoclonal gammopathy was higher than in the group which was negative for monoclonal gammopathy, with a significant difference (Table 4), as reported partially by Kuriakose, et al [26]. No significant difference was found concerning the association between sIFE results and light chain type, which indicates probably that there was no relative underdetection of lambda dominant κ/ λ ratio in our patients as suggested by some authors [14,15]. As the median values of blood creatinine were normal in both normal κ/λ patients and those with abnormal κ/λ ratios, this fact indicates probably an absence of kidney damage that would cause an under-estimation of this ratio [28].…”

“…Nevertheless recently, some other authors [14][15][16][17] have raised doubts about the real usefulness of sFLC, especially since the number of false positives and false negatives compared to serum protein electrophoresis (SPE) and sIFE are quite substantial. In the other hand, many factors can enhance those discrepancies such as renal failure [18], propensity of sFLC (especially those λ) to aggregate or polymerase, which may contributes to underestimation of λ FLC [15], hyper or hypogammaglobulinemia [19].…”

Oligoclonal Pattern/Abnormal Protein Bands in Post-Treatment Plasma Cell Myeloma Patients: Implications for Protein Electrophoresis and Serum Free Light Chain Assay Results

“…As has been reported before, polyclonal increase in gamma globulins tends to favor immunoglobulins with kappa light chains and skewing of the κ/λ ratio in favor of kappa dominance [8, 11, 12, 23, 31]. …”

“…This is further complicated by the under-recognition of lambda chains by SFLCA as has been presented earlier [12]. For example, at first encounter, 90% of the monoclonal gammopathy of undetermined significance (MGUS) lesions with lambda chain monoclonal protein (including those with IgG or other heavy chains) have a falsely normal κ/λ ratio.…”