To help detect, diagnose, and monitor plasma cell disorders (dyscrasias) such as multiple myeloma, primary amyloidosis, and related diseases or to monitor the effectiveness of treatment
Serum Free Light Chains
When you have bone pain, fractures, anemia (with normal size and shape red blood cells (normocytic)), kidney disease, and recurrent infections that your healthcare practitioner suspects are due to a plasma cell disorder; when you are being treated for a plasma cell disorder
A blood sample drawn from a vein in your arm
Light chains are proteins produced by immune cells called plasma cells. Also called kappa and lambda light chains, they link together with other proteins (heavy chains) to form immunoglobulins (also known as antibodies) that target and neutralize specific threats to the body such as bacteria and viruses. Plasma cells normally produce some excess light chains that do not combine with heavy chains and instead enter the bloodstream. Free light chains (FLC) or serum free light chains (SFLC) refer to those that are not part of whole (intact) immunoglobulins and are present in the blood. This test measures the amount of free kappa and lambda light chains in the blood and calculates a kappa/lambda ratio to help detect, diagnose, and monitor conditions associated with an increased production of free light chains.
Each type of immunoglobulin is composed of four protein chains: two identical heavy chains and two identical light chains. A particular plasma cell will produce only one type of immunoglobulin. Normally, there is a slight excess of free light chains produced, so low levels of free kappa and lambda chains are detected in the blood.
With a group of conditions called plasma cell disorders (dyscrasias) or monoclonal gammopathies, a plasma cell becomes neoplastic, dividing more than it should and producing a large number of copies (clones) of itself that crowd out other cells in the bone marrow. Since the clones come from a single plasma cell, they may produce large amounts of the same type of abnormal monoclonal immunoglobulin (M-protein). This may be an intact immunoglobulin, only a light chain, or rarely only a heavy chain.
Excess light chain production may be seen with any of the plasma cell disorders, such as multiple myeloma, MGUS (monoclonal gammopathy of unknown significance, a condition that may progress to multiple myeloma), monoclonal light chain (primary) amyloidosis, and others. These conditions may go unnoticed or may progress to produce various signs and symptoms characteristic of the different diseases.
- How is it used?
Serum free light chain (SFLC) testing is ordered to help detect, diagnose, and monitor plasma cell disorders (dyscrasias), including multiple myeloma, primary amyloidosis, and related diseases or to monitor the effectiveness of treatment.
Light chains are proteins produced by plasma cells. Within a plasma cell, two light chains and two heavy chains combine to form an immunoglobulin.
With a group of conditions called plasma cell disorders or monoclonal gammopathies, a plasma cell becomes neoplastic, dividing more than it should, and produces large amounts of an abnormal monoclonal immunoglobulin (M-protein). This protein may be an intact immunoglobulin or only one of its components – a kappa or lambda light chain, or rarely, a heavy chain.
Plasma cell disorders are routinely diagnosed using serum and urine protein electrophoresis tests (SPEP/UPEP), followed by immunofixation electrophoresis (IFE) tests to determine which immunoglobulin is present in excess. Blood tests may also be ordered to measure levels of intact immunoglobulins (e.g., IgG, IgM, IgA).
Serum free light chain testing provides complementary information. It can detect the excessive free light chains that may be produced by neoplastic plasma cells and changes in the ratio of kappa and lambda production, which indicate an excess of these clonal plasma cells.
Initially, serum free light chain testing is ordered along with a serum protein electrophoresis test to detect abnormal monoclonal protein (M-protein) production and to calculate a kappa/lambda free light chain ratio. If the protein electrophoresis test is abnormal, then an immunofixation electrophoresis test is performed to determine which immunoglobulin is present in excess. If a plasma cell disorder is detected, then the free light chain test may be ordered periodically to monitor the condition or to evaluate the effectiveness of treatment. This test is particularly useful for diagnosing and monitoring select patients who have a less common oligosecretory myeloma, non-secretory myeloma, or light chain-only multiple myeloma.
- When is it ordered?
Serum free light chain testing and a kappa/lambda ratio is ordered along with a protein electrophoresis test when someone has signs and symptoms that a healthcare practitioner suspects are related to a plasma cell disorder. These signs and symptoms will vary from person to person and tend to worsen over time. They involve various parts of the body and may include:
- Bones—bone pain, soft spots, and fractures due to proliferation of plasma cells in the bone marrow
- Blood—anemia (myelophthisic) and frequent infections due to low levels of normal red and white blood cells; plasma cells crowd out the other types of cells in the bone marrow, leading to a decrease of RBCs and WBCs.
- Kidneys—production of abnormal amounts of light chains can lead to increased light chains in the urine (Bence-Jones protein); these proteins can cause kidney damage.
A healthcare practitioner may also order this test when someone has signs and symptoms associated with primary amyloidosis. Amyloidosis develops when abnormal proteins build up in organs or tissue, particularly the heart, liver, kidneys, spleen, gastrointestinal tract, and nervous system. In primary amyloidosis, the proteins are free light chains.
Various other clinical presentations can provide diagnostic clues that a plasma cell disorder may be present. Depending on the plasma cell disorder and which organs are affected, the person may have a variety of symptoms, such as:
- Bone aches
- Weakness, fatigue
- Numbness, weakness or tingling of the arms and legs
- Swelling of ankles and legs
- Shortness of breath, difficulty breathing
- Irregular heartbeat
- Easy bruising
- Purple patches around the eyes (so-called raccoon's eyes)
- Tongue swelling
When a plasma cell disorder is diagnosed, the test may be ordered periodically to monitor the condition and to evaluate the effectiveness of treatment.
- What does the test result mean?
This test must be interpreted in conjunction with other laboratory and clinical findings. A slightly abnormal result does not prove that someone has a plasma cell disorder. Conversely, someone may have a plasma cell disorder despite a normal result from this test. If a person has a plasma cell disorder, the result of this test won't indicate what specific plasma cell disorder is present.
Results of a serum free light chain test will often be evaluated in conjunction with the results of a protein electrophoresis test.
Free light chains will normally be present in the blood at low levels, with a kappa/lambda ratio of approximately 0.26 to 1.65 for individuals with normal kidney function.
Increased kappa free light chains and an increased kappa/lambda ratio may be seen with plasma cell disorders that produce excess monoclonal kappa light chains. Increased lambda free light chains and a decreased kappa/lambda ratio may be seen with plasma cell disorders that produce excess monoclonal lambda light chains.
In the context of MGUS or myeloma, significantly increased free light chain production and a markedly abnormal kappa/lambda ratio indicate an increased risk of disease progression.
When the test is used to monitor a known plasma cell disorder, a decrease in the quantity of excess light chain and a more normal kappa/lambda ratio may indicate a response to treatment.
Increased free light chains and/or an abnormal serum free kappa/lambda ratio may be seen with people who have some degree of kidney dysfunction that is unrelated to a plasma cell disorder. Decreased free light chains with a normal kappa/lambda ratio may be seen with a disorder that suppresses bone marrow cell production.
With suspected primary amyloidosis, an increase in serum free light chains with an abnormal kappa/lambda ratio may suggest that amyloidosis is the cause of symptoms. However, a biopsy of affected tissue establishes the diagnosis.
- Is there anything else I should know?
Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and it usually does not cause symptoms. A minority of people with MGUS will later develop multiple myeloma. This risk is increased in those with increased free light chain production and an abnormal kappa/lambda ratio.
Serum free light chains can also be increased, usually with a normal kappa/lambda ratio, with some connective tissue disorders, inflammatory conditions, neurological conditions, and some cancers but are not typically monitored in people with these conditions.
Serum free light chain analysis accelerates the detection of treatment response because the free light chains have a much shorter half-life (3-5 hours) than intact immunoglobulins (about 21 days). Although it is traditionally used for light chain-only plasma cell disorders, the test is also used for assessing response and minimal residual disease in myelomas that produce intact immunoglobulins.
If someone has this testing done at more than one laboratory, the results may not be interchangeable if the laboratories use different testing methods. If you are having a series of SFLC tests done, it is advised that you have the tests done by the same method, typically by the same laboratory, so that the results can be compared and interpreted correctly. You may wish to discuss this issue with your healthcare practitioner.
- What is primary amyloidosis?
Amyloidosis is a condition that occurs when abnormal proteins, called amyloids, are produced and deposited in various organs in the body, causing tissue and organ damage. This is a rare, progressive disorder that can affect one or more organs, including the heart, liver, kidneys and gastrointestinal tract.
The amyloidosis disorders can be divided by types of amyloid protein, primary (clonal) versus secondary (reactive), and acquired versus hereditary. Primary amyloidosis is the most common form and is sometimes seen in association with MGUS or multiple myeloma. It results from the deposition of whole or fragments of immunoglobulin light chains (known as AL amyloid) secreted by clonal plasma cells into various organs and tissues. The deposition of this material typically results in organ dysfunction.
- Should everyone have a serum free light chain test?
No. This test is not intended to be a screen for the general public. It may be useful as part of the evaluation of certain individuals with unexplained signs or symptoms that could be due to a plasma cell disorder.
- Why would my healthcare practitioner order a "baseline" serum free light chain test?
If you have monoclonal gammopathy of undetermined significance (MGUS) or are diagnosed with another plasma cell disorder (dyscrasia), then a serum free light chain test and ratio done when you are diagnosed and/or prior to any treatment can be used to compare with subsequent testing to help assess disease progression or response to treatment.
- Can serum free light chain testing be done at home or in my healthcare practitioner's office?
No. This test is not available for home testing. It requires specialized equipment and is usually performed in a laboratory. Your sample may need to be sent to a reference laboratory.