Replacing Urine Protein Electrophoresis With Serum Free Light Chain Analysis as a First-line Test for Detecting Plasma Cell Disorders Offers Increased Diagnostic Accuracy and Potential Health Benefit to Patients

Malcolm P. McTaggart, PhD; Jindriska Lindsay, FRCPath; Edward M. Kearney, FRCPath


Am J Clin Pathol. 2013;140(6):890-897. 

In This Article

Abstract and Introduction


Objectives To determine the most clinically effective diagnostic testing strategy for plasma cell disorders in the clinical laboratory.

Methods Serum and urine samples from 2,799 patients with suspected plasma cell dyscrasias were tested by alternative diagnostic testing strategies consisting of serum protein electrophoresis (SPE) with either urine protein electrophoresis (UPE) or serum free light chain (sFLC) analysis.

Results The combination of sFLC analysis and SPE had the greatest sensitivity (100%), detecting abnormalities in all 124 patients diagnosed with plasma cell disorders. Routine sFLC testing would have had much potential health benefit for two patients in the study population. First, a patient who had a markedly abnormal sFLC result was diagnosed with light chain deposition disease by renal biopsy, but no abnormality was detected by SPE or UPE. Second, a patient diagnosed with multiple plasmacytomas following biopsy of a lung tumor had a grossly abnormal sFLC result but an equivocal weak-positive SPE result, and no urine sample was received by the laboratory for the patient.

Conclusions Our study suggests that the combination of SPE and sFLC analysis is the most clinically effective first-line diagnostic testing strategy for detecting plasma cell disorders in the clinical laboratory.


Multiple myeloma (MM) is a malignant disease of bone marrow plasma cells that has an annual incidence of 5.6 cases per 100,000 people in the Western world.[1] The diagnosis of MM and related plasma cell disorders often takes longer than is desirable following first presentation to primary care;[2] therefore, there is a need to improve the testing strategy for these diseases.

The detection and quantification of monoclonal proteins (M-proteins) is central to the diagnosis and monitoring of MM.[3–7] In addition to MM, M-proteins may be present in other B-cell neoplasms, such as monoclonal gammopathy of undetermined significance (MGUS), amyloid light chain (AL) amyloidosis, plasmacytomas, leukemias, and lymphomas. Rather than conferring a specific diagnosis, the detection of M-proteins is an indication for further investigation.

To detect intact M-proteins, many researchers use serum protein electrophoresis (SPE), followed by serum immunofixation electrophoresis if an abnormality is detected.[3–7] This is universally accepted as the most effective approach for detecting intact M-proteins in the clinical laboratory. However, SPE is inadequate for the detection of light chain, oligosecretory, and nonsecretory MM, as well as other plasma cell disorders (eg, AL amyloidosis and light chain deposition disease).

There has been much debate in recent years as to the most effective method for detecting monoclonal free light chains (FLCs),[8–11] which are present in approximately 80% of patients with MM and are the only detectable M-protein in 20% of those with the disease.[12] Traditionally, urine protein electrophoresis (UPE) has been used to detect FLCs in urine, termed Bence-Jones protein (BJP).[13] The sensitivity of this method is limited due to reabsorption of FLCs in the renal tubules, meaning FLCs may not reach the urine until loss of tubular function has occurred.[14] There are also well-recognized practical problems with getting urine samples sent to the laboratory for patients being tested for plasma cell disorders: compliance for urine accompanying the serum sample in this setting has ranged from 5% to 40% in different studies.[15–17]

A novel test (serum free light chain [sFLC] analysis) for detecting increased concentrations of immunoglobulin light chains was described in 2001.[18] A number of studies have assessed the use of sFLC analysis in the detection of plasma cell disorders.[15–17,19–25] Most studies have found that sFLC testing has superior diagnostic sensitivity to UPE for detecting plasma cell dyscrasias, particularly AL amyloidosis, light chain deposition disease, and nonsecretory MM.[15–17,19–23,25] However, the modestly high false-positive rate and variable analytical performance of sFLC testing have been highlighted in the literature, particularly the reported high coefficients of variation of the assays.[7,11,24–26] Nevertheless, International Myeloma Working Group guidelines now recommend use of the sFLC assays as a first-line test for MM and related plasma cell disorders.[5] United Kingdom clinical guidelines advocate use of the sFLC assays only once a monoclonal protein has been identified, as well as for detection and monitoring of nonsecretory MM and AL amyloidosis.[4,6]

Previous studies have assessed the diagnostic accuracy of sFLC testing, but there has been limited analysis of their clinical utility, which is the most important consideration when evaluating a diagnostic test.[27] The aim of this prospective study was to determine the relative clinical benefit of a first-line testing strategy of SPE and UPE compared with that of SPE and sFLC analysis.