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

Abstract

BackgroundQuantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies.MethodsResults of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively.ResultsThe κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances.ConclusionsThe lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

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

“…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]. But the point still remaining is that sFLC measurement has the same utility and impact on MM diagnosis and monitoring.…”

Multiple myeloma: Detection of free monoclonal light chains by modified immunofixation electrophoresis with antisera against free light chains

“…In one such patients with kappa dominant kappa/lambda ratio, for example, sample #42, detection of monoclonal lambda light chain and lack of detection of monoclonal kappa chain by FLC-Modified SIFE is likely to be due to high levels of kappa light chains being all polyclonal while all, or most, of the lambda light chains being monoclonal. The post-ASCT treatment abundance of polyclonal kappa light chains, including in patients with lambda light chain associated lesions, has been documented earlier [ 20 , 23 ].…”

“…This excess production of light chains extends to NMG. In neoplastic disorders of plasma cells, serum and urine contain free monoclonal light chains and these can serve as diagnostic and monitoring tools for NMG [ [18] , [19] , [20] ]. In LCMM and LCPMM, measuring and monitoring of SFLC provides a practical method for monitoring the course of disease [ 13 , 19 ].…”