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In my previous post, we talked about the structure of the immunoglobulin.
I’d like to now do a slightly deeper dive into the light chain part of the immunoglobulins- kappa and lambda.
I think this is important because as a hematologist, I see many referrals for “monoclonal gammopathy” based only on the serum protein electrophoresis (SPEP) and it would be hugely helpful to get the kappa/lambda light chains upfront.
Serum kappa and lambda are light chain proteins produced by plasma cells as part of normal immunoglobulin (antibody) production. Each antibody molecule contains either kappa or lambda light chains, but never both.
In healthy individuals, the ratio of kappa to lambda light chains in serum typically falls between 0.26 and 1.65.
Measuring serum free light chains (sFLC) and calculating the kappa/lambda ratio is clinically valuable for detecting and monitoring plasma cell disorders such as multiple myeloma, AL amyloidosis, and other monoclonal gammopathies.
An abnormal ratio—either elevated or reduced—suggests clonal proliferation of plasma cells producing excess amounts of one light chain type, which can indicate underlying disease or help assess treatment response in patients with confirmed plasma cell dyscrasias.
Approximately 15-20% of multiple myeloma cases are light chain only disease, also known as light chain myeloma. In these cases, the malignant plasma cells produce only free light chains (either kappa or lambda) without producing complete immunoglobulin molecules that include heavy chains. This is in contrast to the majority of myeloma cases (~60-70%) where intact immunoglobulins are produced, and a small percentage (~2-3%) that are non-secretory, producing neither complete antibodies nor detectable light chains.
Light chain myeloma is clinically significant because these smaller light chain proteins are more readily filtered through the kidneys, which can lead to increased risk of renal complications and makes urine testing (for Bence Jones protein) particularly important for diagnosis and monitoring alongside serum free light chain assays.
Therefore, if you’re suspecting a monoclonal gammopathy based on high total protein on the SPEP, I strongly encourage you to simultaneously order serum free kappa/lambda light chain assay. This can fastrack triage in a hematology referral work queue because if there is a monoclonal light chain on serum with serum free light chain ratio (involved/uninvolved) >100, that meets criteria for diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG)
Here are the causes of increased serum light chains, classified by whether they produce polyclonal or monoclonal elevations:
Monoclonal Light Chain Elevations (abnormal κ/λ ratio):
Multiple myeloma (including light chain myeloma),
Waldenström macroglobulinemia,
AL (light chain) amyloidosis,
monoclonal gammopathy of undetermined significance (MGUS),
solitary plasmacytoma,
light chain deposition disease,
chronic lymphocytic leukemia (CLL) with monoclonal protein, other B-cell lymphomas with monoclonal component, and heavy chain diseases.
Polyclonal Light Chain Elevations (normal κ/λ ratio):
Chronic kidney disease and renal impairment (decreased clearance of light chains),
autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome,
chronic inflammatory conditions,
chronic liver disease,
congestive heart failure,
acute infections and sepsis,
HIV infection
The key distinction is that monoclonal elevations indicate clonal plasma cell or B-cell proliferation and produce an abnormal kappa/lambda ratio, while polyclonal elevations reflect either decreased clearance or reactive increases in overall antibody production and maintain a normal kappa/lambda ratio. This makes the κ/λ ratio essential for distinguishing benign polyclonal increases from pathologic monoclonal processes.
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