What is being tested?
The test measures the amount of free kappa and lambda light chains in the blood and calculates a kappa/lambda ratio. It does this to help detect, diagnose, and monitor conditions associated with an increased production of free light chains (FLC).
Kappa and lambda light chains are components of immunoglobulin proteins ("Antibodies") which are normally produced by specialised antibody producing cells called plasma cells. Immunoglobulins are the antibodies that target and neutralize specific threats to the body, such as bacteria and virus.
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 can be detected in the blood.
With a group of conditions called plasma cell disorders (dyscrasias) or monoclonal gammopathies, a plasma cell becomes malignant, dividing uncontrollably 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 produce large amounts of the same type of abnormal monoclonal immunoglobulin (M-protein). This may take the form of an intact immunoglobulin, a light chain, or rarely a heavy chain. Excess light chain production may be seen with any plasma cell disorder, such as multiple myeloma, MGUS (monoclonal gammopathy of unknown significance – a condition that may progress to multiple myeloma), and monoclonal light chain (primary) amyloidosis (see Common questions above). In the beginning, these conditions may cause few symptoms, but as time progresses, they can cause bone pain and fractures, anaemia, fatigue, weight loss, and kidney dysfunction.
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 clone of plasma cells. 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 signs and symptoms related to a plasma cell disorder. Some of the signs and symptoms can involve various parts of the body:
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:
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 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 biopsy of affected tissue is the primary means of establishing 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 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).
Common questions
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 and 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.
This test is not intended to be a screen for the general public; it is intended to detect excess monoclonal free light chain production. Most people will not need to have this test done.
If you have monoclonal gammopathy of undetermined significance (MGUS) or are diagnosed with another light chain plasma cell disorder (dyscrasia), then a 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 – for signs of disease progression or response to treatment.
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.
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