Test Catalog

Test ID: FLCS    
Immunoglobulin Free Light Chains, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring serum from patients with monoclonal light chain diseases without a M-spike on protein electrophoresis


May be useful as a diagnostic test in patients in whom there is a suspicion of primary systemic amyloidosis, light chain deposition disease, or non-secretory myeloma

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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. The monoclonal immunoglobulin 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 macroglobulinemia (WM), nonsecretory multiple myeloma (NSMM), smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis (AL), and light chain deposition disease (LCDD). 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 serum protein electrophoresis.


An elevated ratio of kappa to lambda free light chains (FLC K/L) indicates a monoclonal kappa FLC, and an abnormally low FLC K/L indicates a monoclonal lambda FLC. The kappa and lambda FLC may both be elevated in the sera of patients with polyclonal hypergammaglobulinemia, but the FLC K/L is normal. If a patient has an abnormal serum FLC K/L ratio but has no serum monoclonal protein detected by immunofixation, a urine monoclonal protein study (eg, immunofixation) should be performed and the serum immunofixation should be repeated.


The FLC K/L ratio may be useful as a diagnostic test for patients in whom immunofixation for serum monoclonal light chains is negative and in whom there is a suspicion of primary systemic amyloidosis, light chain deposition disease, or non-secretory myeloma.


The quantitation of kappa or lambda immunoglobulin free light chains may be used to monitor disease activity in patients with monoclonal light chain diseases without a serum M-spike.


The following algorithms are available in Special Instructions:

-Laboratory Approach to the Diagnosis of Amyloidosis

-Laboratory Screening Tests for Suspected Multiple Myeloma

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.


0.33-1.94 mg/dL



0.57-2.63 mg/dL




Interpretation Provides information to assist in interpretation of the test results

The specificity of this assay for detection of monoclonal light chains relies on the ratio of free kappa and lambda (K/L) 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 more than 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 (K/L) 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.

This assay has not been established for use with the pediatric population.   

Moderate-to-marked lipemia may interfere with the ability to perform testing.

Supportive Data

Studies at Mayo Clinic have shown that in some patients with urine monoclonal light chains and negative serum immunofixation (IF), the free light chain (FLC) assay can identify monoclonal FLC in the serum. These studies support the increased sensitivity of the nephelometric FLC assay. In a series of patients with primary systemic amyloid treated by stem cell transplantation, the quantitation and monitoring of FLC predicted organ response (eg, disease course).

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Kaleta E, Kyle R, Clark R, Katzmann J: Analysis of patients with gamma-heavy chain disease by the heavy/light chain and free light chain assays. Clin Chem Lab Med. 2014 May;52(5): 665-669. doi: 10.1515/cclm-2013-0714

2. Palladini G, Russo P, Bosoni T, et al: Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009 Mar;55(3):499-504. doi: 10.1373/clinchem.2008.117143

3. Dispenzieri A, Kyle R, Merlini G, et al: International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009 Feb;23(2):215-224. doi: 10.1038/leu.2008.307

4. Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR: Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood. 2001 May;97(9):2900-2902

Special Instructions Library of PDFs including pertinent information and forms related to the test