Serum Free Light Chains: Optimal Testing Recommendations

  • Screening: Order with serum protein electrophoresis and immunofixation for patients suspected of having a malignant monoclonal process: multiple myeloma (MM), Waldenström macroglobulinemia, B-cell lymphoproliferative process, AL amyloidosis. Note: this is an alternative that relieves the need for a urine specimen in the older standard of serum protein electrophoresis with immunofixation and urine immunofixation.
  • Prognosis: Use this as a baseline measurement to assess risk of all plasma cell disorders
  • Monitoring: Use to determine complete stringent remission
  • Monitoring: Order to follow patients with oligosecretory multiple myeloma and an abnormal serum free light chain ratio
  • Monitoring: Order to follow AL amyloidosis with an abnormal serum free light chain ratio
  • Note: the International Myeloma Working Group recommends 24 hour urine protein electrophoresis, not serum free light chains, to follow patients with multiple myeloma

Guidelines for Test Utilization

What does the test tell me?

The serum free light chain test measures the quantity of unbound immunoglobulin kappa and lambda light chain molecules in the serum. The ratio of the serum free kappa to serum free lambda is useful for detecting and following a monoclonal free light chain process. [back to top]

When should I order this test?

Features such as increased calcium, anemia, renal disease, bone pain or bone lesions that are suspicious for an underlying plasma cell disorder. The most common disorders considered are: multiple myeloma, Waldenström macroglobulinemia, AL amyloidosis, plasmacytoma and monoclonal gammopathy associated neuropathies. [back to top]

When should I NOT order this test?

This test should not be ordered unless there is a known, or suspicion of a monoclonal disorder. [back to top]

How should I interpret the result?

If the serum free kappa and lambda are in the reference interval and the ratio of serum free kappa/serum free lambda is in the reference interval, the test does not support the presence of a monoclonal gammopathy.

When only one of the serum free light chains is increased and the ratio of serum free kappa/serum free lambda is outside of the reference interval, it is evidence supporting the presence of a monoclonal gammopathy.

When both serum free light chains are elevated and the ratio of serum free kappa/serum free lambda is either within the reference interval or only slightly increased, this may indicate the presence of renal disease or chronic inflammation. [back to top]

Is the test result diagnostic/confirmatory of the condition? If not, is there a diagnostic/confirmatory test?

No. Whereas an abnormal result can support the diagnosis of a monoclonal gammopathy, demonstration of a monoclonal spike in the serum or urine by protein electrophoresis and immunofixation provide more definitive proof of the presence of a monoclonal process. [back to top]

Are there factors that can affect the lab result?

Patients with renal disease and/or chronic inflammation may have an increase in one or both of the serum free light chains and there may be a modest increase in the ratio of serum free kappa/serum free lambda.

If there is a marked increase in one of the serum free light chains, this may yield a falsely low value due to a phenomenon called the high-dose hook effect, also known as antigen excess effect. [back to top]

Are there considerations for special populations?

Monoclonal gammopathies are rare in children; their occurrence gradually increases with age. [back to top]

What other test(s) might be indicated?

This test is usually performed together with serum protein electrophoresis, immunofixation and quantification of total IgG, IgA and IgM. [back to top]

References

Dispenzieri A, et al. Leukemia 23;215, 2009.

Graziani MS and Merlini G. Expert Rev Mol Diagn 14;55, 2014.

Genzen JR, et al. Arch Pathol Lab Med doi: 10.5858/1401.2017-0128-CP

Rajkumar SF et al. Blood 117;4691, 2011.

Larson D, et al. NEJM (letter) 367:581, 2012

Khoriaty R et al. Clin Lymophoma Myeloma Leuk 10:E10-E13, 2010

Kumar SK, et al. Mayo Clin Proc 79:867, 2004.

Abadie JM et al. Clin Chem 131:166, 2009.

Singh G. Am J Clin Pathol 146:207, 2016.


Last reviewed: June 2020. The content for Optimal Testing: AACC's Guide to Lab Test Utilization has been developed and approved by the AACC Academy and AACC's Science and Practice Core Committee.

As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients received the highest quality and most useful laboratory tests. AACC's Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.