From the Guidelines
Elevated kappa and lambda free light chains are primarily caused by plasma cell disorders, such as multiple myeloma, and kidney dysfunction, as evidenced by the most recent study 1. The causes of elevated kappa and lambda free light chains can be understood by examining the underlying pathophysiology of plasma cell disorders and the role of the kidneys in filtering and metabolizing these proteins.
Plasma Cell Disorders
In plasma cell disorders like multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and certain lymphomas, abnormal plasma cells produce excess immunoglobulin light chains that aren't attached to heavy chains, leading to elevated levels of kappa and lambda free light chains in the blood 1.
Kidney Dysfunction
Kidney disease can also cause elevated free light chains because these proteins are normally filtered and metabolized by the kidneys; when kidney function declines, both kappa and lambda chains increase but typically maintain a normal ratio 1.
Other Conditions
Other conditions that may cause elevated free light chains include chronic inflammation, autoimmune diseases, and certain infections, though these typically cause polyclonal increases with a normal kappa/lambda ratio 1.
Diagnostic Importance
Measuring free light chains is valuable for diagnosing and monitoring plasma cell disorders, with persistent abnormalities suggesting active disease requiring treatment, as highlighted in the updated criteria for the diagnosis of multiple myeloma 1. Some key points to consider when evaluating elevated kappa and lambda free light chains include:
- The ratio of kappa to lambda chains is often more diagnostically important than absolute values, with an abnormal ratio suggesting a monoclonal process 1.
- The presence of myeloma-defining events, such as end-organ damage or high-risk cytogenetics, can help distinguish between smoldering and active multiple myeloma 1.
- Clinical trials and participation in research studies are essential for advancing the understanding and management of plasma cell disorders 1.
From the Research
Causes of Elevated Kappa and Lambda Free Light Chains
Elevated kappa and lambda free light chains can be caused by various conditions, including:
- Monoclonal gammopathies, such as multiple myeloma and Waldenström's macroglobulinemia 2, 3, 4
- Lymphomas, including diffuse large B-cell lymphoma, Hodgkin lymphoma, and chronic lymphocytic leukemia 2
- Autoimmune diseases, such as systemic lupus erythematosus, myasthenia gravis, systemic sclerosis, rheumatoid arthritis, and Sjögren's syndrome 5
- Amyloidosis, a condition characterized by the deposition of abnormal proteins in tissues 3, 6
Types of Elevations
Elevations in kappa and lambda free light chains can be either:
- Monoclonal, indicating the presence of a single clone of plasma cells producing a specific type of immunoglobulin 2, 4
- Polyclonal, indicating the presence of multiple clones of plasma cells producing different types of immunoglobulins 2, 5
Clinical Significance
Elevated kappa and lambda free light chains can be associated with: