From the Guidelines
Elevated kappa and lambda light chains in the blood are a strong indicator of a plasma cell disorder, such as multiple myeloma, and require immediate evaluation by a hematologist or oncologist. The diagnostic workup for this condition should include serum protein electrophoresis, immunofixation, and quantification of immunoglobulins IgG, IgA, and IgM, as well as characterization of the heavy and light chains by immunofixation 1.
Key Diagnostic Steps
- Serum protein electrophoresis and urine protein electrophoresis (concentrate of 24-h urine) to detect and evaluate the monoclonal (M-) component
- Quantification of Immunoglobulins IgG, IgA, and IgM to assess the level of immunoglobulin components
- Characterization of the heavy and light chains by immunofixation to determine the type of plasma cell disorder
- Serum-free light-chain measurement for identifying and monitoring nonsecretory multiple myeloma (MM) 1
Additional Evaluations
- Evaluation of bone marrow plasma-cell infiltration through bone marrow aspiration and biopsy to detect quantitative and/or qualitative abnormalities of bone marrow plasma cells
- Evaluation of lytic bone lesions through full skeleton X-ray survey, with optional magnetic resonance imaging (MRI) for greater details, especially if spinal cord compression is suspected 1
Treatment Considerations
Treatment depends on the underlying cause, with MGUS typically requiring monitoring every 6-12 months, while multiple myeloma treatment may involve combinations of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and steroids. The ratio between kappa and lambda chains is crucial diagnostically, and elevated levels of both types may indicate polyclonal activation as seen in inflammatory conditions rather than a malignant process.
From the Research
Elevated Kappa and Lambda Light Chain in Blood
Elevated kappa and lambda light chains in blood can be an indicator of various conditions, including monoclonal gammopathies.
- The serum free light chain test is used to detect and monitor these conditions, and it has been shown to be more sensitive than urine electrophoresis for monitoring monoclonal gammopathies 2.
- However, the test may not always be accurate, and the kappa/lambda ratio may be abnormal less frequently in lambda chain lesions 3.
- The underproduction of free lambda light chains can also lead to under-detection of lambda dominant kappa/lambda ratio in some patients 3.
Diagnosis and Monitoring
The diagnosis and monitoring of monoclonal gammopathies involve various laboratory methods, including serum and urine protein electrophoresis, immunofixation electrophoresis, and serum-free light chain assays.
- These methods should be used in an algorithmic approach to avoid unnecessary testing, and the results should be tailored to the clinical context of each individual patient 4.
- The serum-free light chain assay has shortcomings, and new assays for measuring monoclonal serum free light chains are being developed 4.
- Urine testing is also useful in the diagnosis and monitoring of light chain only lesions, and a new method of measuring monoclonal serum-free light chains has been introduced 4.
Clinical Significance
The clinical significance of abnormal serum kappa/lambda light chain ratio in patients with chronic kidney disease has been evaluated.
- The study found that an abnormal kappa/lambda ratio is a common and nonspecific finding in patients with proteinuria or chronic kidney disease of unknown origin 5.
- The ratio did not correlate with age, proteinuria, or estimated glomerular filtration rate, and it was not a specific marker for multiple myeloma 5.
- However, the detection of monoclonal free light chains in urine can serve as a marker of minimal residual disease in multiple myeloma, and a new method of urine immunofixation has been developed to detect these chains 6.