Immunoglobulin Free Light Chains, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The monoclonal gammopathies are characterized by a clonal expansion of plasma cells that secrete a monoclonal immunoglobulin (Ig). The monoclonal Ig secreted by these cells serves as a marker of the clonal proliferation, and the quantitation of monoclonal protein can be used to monitor the disease course.
The monoclonal gammopathies include multiple myeloma (MM), light chain multiple myeloma (LCMM), Waldenstrom’s macroglobulinemia (WM), nonsecretory myeloma (NSMM), smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis (AL), and light chain deposition disease (LCDD).
Monoclonal proteins are typically detected by serum protein electrophoresis (SPEP) and immunofixation (IF). However, the monoclonal light chain diseases (LCMM, AL, LCDD) and NSMM often do not have serum monoclonal proteins in high enough concentration to be detected and quantitated by SPEP.
A sensitive nephelometric assay specific for kappa free light chain (FLC) that doesn’t recognize light chains bound to Ig heavy chains has recently been described. This automated, nephelometric assay is reported to be more sensitive than IF for detection of monoclonal FLC. In some patients with NSMM, AL, or LCDD the FLC assay provides a positive identification of a monoclonal serum light chain when the serum IF is negative. In addition, the quantitation of FLC has been correlated with disease activity in patients with NSMM and AL.
See Laboratory Approach to the Diagnosis of Amyloidosis and Laboratory Screening Tests for Suspected Multiple Myeloma in Special Instructions.
Monitoring patients with monoclonal light chain diseases but no M-spike on protein electrophoresis
The specificity of this assay for detection of monoclonal light chains relies on the ratio of free kappa and lambda light chains. Once an abnormal free light chain (FLC) K/L ratio has been demonstrated and a diagnosis has been made, the quantitation of the monoclonal light chain is useful for monitoring disease activity.
Changes in FLC quantitation reflect changes in the size of the monoclonal plasma cell population. Our experience to date is limited, but changes of >25% or trending of multiple specimens are needed to conclude biological significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Elevated kappa and lambda free light chain (FLC) may occur due to polyclonal hypergammaglobulinemia or impaired renal clearance. A specific increase in FLC (eg, FLC K/L ratio) must be demonstrated for diagnostic purposes.
Moderate to marked lipemia may interfere with the ability to perform testing.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
KAPPA-FREE LIGHT CHAIN
LAMBDA-FREE LIGHT CHAIN
KAPPA/LAMBDA FLC RATIO
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Drayson M, Tang LX, Drew R, et al: Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97(9):2900-2902