How is it used?
Free light chain testing is ordered to help detect, diagnose, and monitor plasma cell disorders (dyscrasias), including primary amyloidosis (see Common questions above), and to monitor the effectiveness of treatment.
Traditionally, plasma cell disorders have been 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 be ordered to measure levels of intact immunoglobulins (IgG, IgM, IgA).
Free light chain testing provides complementary information. It can detect the low levels of free light chains that are sometimes all that is produced by a plasma cell disorder and can detect changes in the ratio of kappa and lambda production, which indicate an excess of one of . Initially, the test 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 light chain disorder is detected, then the free light chain test may be ordered periodically to monitor the condition and to evaluate the effectiveness of treatment.
When is it requested?
Free light chain testing and a kappa/lambda ratio is ordered along with a protein electrophoresis test when a doctor suspects that a person has and related to a plasma cell disorder. Some of the signs and symptoms can involve various parts of the body:
- Bones—bone pain, soft spots, and fractures due to proliferation of in the
- Blood—anaemia and frequent infections due to low levels of 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 lodge or deposit in the kidneys, causing damage.
A doctor may also order this test if a patient has signs and symptoms associated with primary amyloidosis (see Common questions above). 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. Depending on the organs affected, the person may have a variety of symptoms such as:
- Swelling of ankles and legs
- Weakness, fatigue
- Numbness, weakness or tingling of the arms and legs
- Shortness of breath, difficulty breathing
- An irregular heartbeat
- Easy bruising
- Purple patches around the eyes (so-called raccoon's eyes)
- Persistent increase in tongue size
When a light chain 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?
Results of a 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, but with a normal kappa/lambda ratio.
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 general, significantly increased free light chain production and an abnormal kappa/lambda ratio indicate a poorer prognosis and an increased risk of disease progression.
When the test is used to monitor a known light chain plasma cell disorder, then a decrease in the quantity of excess light chain and a more normal kappa/lambda ratio indicates a response to treatment.
Increased concentrations with a normal kappa/lambda ratio may be seen with people who have some degree of kidney dysfunction that is unrelated to a plasma cell disorder. Kidney disease can also slightly alter the ratio of free kappa/lambda. 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 patients with these conditions.
Decreased concentrations with a normal kappa/lambda ratio may be seen with a disorder that suppresses bone marrow cell production.
With suspected primary amyloidosis (see Common questions above), an increase in free light chains with an abnormal kappa/lambda ratio may suggest that amyloidosis is the cause of symptoms. However, a of affected tissue is the primary means of establishing the diagnosis.
Is there anything else I should know?
Monoclonal gammopathy of undetermined significance () is the most common plasma cell disorder and it usually does not cause symptoms. A percentage 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.
Free light chain analysis accelerates the detection of treatment response due to the much shorter half-life (3-5 hours versus 21 days for intact immunoglobulin). Although it is traditionally used for light chain-only plasma cell disorders, the test has increasingly been used for treatment monitoring of myelomas that produce intact immunoglobulins (e.g., IgG, IgA).