From the Guidelines
Kappa and lambda light chains are crucial in diagnosing and monitoring plasma cell disorders, such as multiple myeloma, with an abnormal ratio suggesting a clonal plasma cell disorder, as defined by the International Myeloma Working Group (IMWG) criteria 1.
Importance of Kappa and Lambda Light Chains
Kappa and lambda light chains are proteins that form part of antibodies in the human body, with each antibody consisting of two heavy chains and two light chains. In healthy individuals, the ratio of kappa to lambda light chains in serum is approximately 2:1, with kappa being more abundant.
- These light chains play crucial roles in immune function by helping antibodies recognize and bind to specific antigens.
- When plasma cells become abnormal, as in conditions like multiple myeloma or amyloidosis, they may produce excess free light chains that can be detected in blood and urine.
Diagnostic and Monitoring Tool
Measuring kappa and lambda free light chains and their ratio is an important diagnostic tool for plasma cell disorders, with an abnormal ratio suggesting a clonal plasma cell disorder, as defined by the IMWG criteria 1.
- The test is particularly useful for monitoring disease progression and response to treatment in patients with plasma cell disorders, as changes in free light chain levels often reflect disease activity.
- According to the IMWG criteria, a normal FLC ratio is defined as 0.26-1.65, and a stringent complete response (sCR) is defined as a normal FLC ratio and absence of clonal cells in bone marrow, among other criteria 1.
Clinical Application
In clinical practice, the measurement of kappa and lambda free light chains is essential for diagnosing and monitoring plasma cell disorders, and for assessing response to treatment.
- The IMWG criteria provide a standardized framework for evaluating response to treatment and disease progression in patients with multiple myeloma, with a focus on the measurement of kappa and lambda free light chains and their ratio 1.
From the Research
Kappa Lambda Light Chains
- Kappa lambda light chains are components of immunoglobulins, with kappa light chains representing approximately 2/3 of the light chains of total immunoglobulins 2.
- The kappa/lambda ratio is used to diagnose and monitor monoclonal gammopathies, including multiple myeloma 3, 4, 5.
- An abnormal kappa/lambda ratio can be a common finding in patients with proteinuria or chronic kidney disease of unknown origin, but it may not be specific to multiple myeloma 4.
- Serum free light chain (sFLC) testing can provide greater sensitivity than urine electrophoresis for monitoring multiple myeloma, especially in patients with light chain only lesions 3, 5.
- The sFLC kappa/lambda ratio can be used to suspect multiple myeloma in patients with unexplained bone lesions, even if serum and urine immunofixation electrophoresis results are negative and light chain ratio is normal 5.
Diagnosis and Monitoring
- Serum and urine protein electrophoresis, immunofixation electrophoresis, and sFLC assays are commonly used laboratory methods for diagnosis and monitoring of monoclonal gammopathies 6.
- The choice of test method and interpretation of results should be tailored to the clinical context of each individual patient 6.
- Caution is urged in the interpretation of results of sFLC assay, kappa/lambda ratio, and myeloma defining conditions, especially in patients with oligoclonal bands or those who have undergone hematopoietic stem cell transplants 6.
Immunoglobulin K Light Chain Deficiency
- Immunoglobulin K light chain deficiency is a rare humoral immune defect that can cause serious recurrent bacterial infections 2.
- The genetic basis of this defect has been explored in only a few cases, and it is likely that this defect is underestimated 2.
- Studies have shown that a homozygous mutation in the constant region of the kappa chain can cause abnormal folding of the kappa chain, leading to a defect in the antibody repertoire 2.