What is S-FLC Lambda?
S-FLC Lambda is a biomarker that measures the concentration of free lambda immunoglobulin light chains in serum. Lambda chains are part of the body's immunoglobulins, i.e. the antibodies produced by B lymphocytes and plasma cells. Immunoglobulins consist of two heavy and two light chains. The light chains are either of the kappa or lambda type. During normal antibody production, a small excess of light chains is formed that are not bound to complete immunoglobulins. These circulate freely in the blood and are called free light chains, FLC.
Why is S-FLC Lambda analyzed?
S-FLC Lambda is analyzed together with S-FLC Kappa and to assess the production and balance between free immunoglobulin light chains.
The analysis is primarily used as a complement in the investigation and follow-up of conditions in which a group of plasma cells produces a disproportionately large amount of a certain type of immunoglobulin or free light chain. It can occur in, among other things:
- AL amyloidosis
- multiple myeloma
- light chain myeloma
- MGUS, monoclonal gammopathy of undetermined significance
- other monoclonal gammopathy and plasma cell diseases
FLC analysis is often used in conjunction with serum protein fractions and immunofixation. Free light chains can sometimes be present without a clear M component seen in traditional serum protein analysis.
How is an elevated S-FLC Lambda interpreted?
An elevated S-FLC Lambda means that the concentration of free lambda chains is above the laboratory's reference interval. For the current analysis method, a reference interval of 8.3–27.0 mg/L is specified. The result should always be assessed together with free kappa chains, the kappa/lambda ratio and kidney function.
If both kappa and lambda are elevated while the kappa/lambda ratio is relatively preserved, this may be due to a polyclonal increase in immunoglobulin production. Such a pattern can be seen in, for example, infection, inflammation, autoimmune disease or impaired kidney function.
If, on the other hand, the lambda chains are clearly elevated and the kappa/lambda ratio is at the same time pathologically shifted towards lambda, this may indicate monoclonal production of free lambda chains. This can occur in, for example, MGUS, myeloma or other plasma cell diseases.
What does a low kappa/lambda ratio mean?
describes the ratio between free kappa chains and free lambda chains. In the case of a relative overproduction of lambda, the ratio decreases because the amount of lambda becomes high in relation to kappa. A clearly reduced kappa/lambda ratio together with an elevated S-FLC Lambda can therefore increase the suspicion of a monoclonal production of lambda chains. The ratio is often more diagnostically informative than an isolated elevated lambda value.
However, an abnormal ratio does not in itself mean that a malignant plasma cell disease is present. The result needs to be assessed together with the absolute levels of both chains and other laboratory findings.
How does kidney function affect S-FLC Lambda?
Free light chains are eliminated mainly via the kidneys. In case of impaired renal function, excretion decreases and both kappa and lambda can accumulate in the blood. An elevated S-FLC Lambda does not therefore have to be due to monoclonal production. Creatinine and eGFR are important supplementary values in the interpretation, and reference limits for the kappa/lambda ratio may need to be assessed differently in case of pronounced renal function impairment.
What does a low S-FLC Lambda mean?
A low value of free lambda chains usually has less clinical significance than an elevated value or a clearly deviating kappa/lambda ratio. Low levels can occur, among other things, in cases of reduced immunoglobulin production or immunosuppression.
A low lambda value can also contribute to an elevated kappa/lambda ratio and therefore always needs to be assessed in relation to the level of free kappa chains.
S-FLC Lambda together with Kappa and the ratio
S-FLC Lambda should not be interpreted as a standalone biomarker. The diagnostic information becomes significantly greater when lambda is analyzed together with S-FLC Kappa and .
In the blood sample Free immunoglobulin chains (FLC), all three components are analyzed. This makes it possible to assess both the absolute concentrations and the balance between kappa and lambda, which is central to distinguishing a possible monoclonal production from more general changes in immunoglobulin production.
What other samples can be assessed together with S-FLC Lambda?
When monoclonal gammopathy is suspected, FLC is often used together with other laboratory analyses, for example:
- creatinine and eGFR
- serum protein fractions or serum eluphoresis
- immunoglobulins IgG, IgA and IgM
- hemoglobin and other blood status
- calcium
When questioning AL amyloidosis or certain other plasma cell diseases, additional analyses of serum and urine may also be needed.
Analysis method and reference interval
S-FLC Lambda is analyzed using an immunochemical method, usually nephelometry. The result is given in mg/L. The reference range varies between laboratories and analysis methods. For the current method, 8.3–27.0 mg/L is specified for S-Lambda chain, free. The reference range specified on the current laboratory result should always be used when interpreting.
Important to know
An elevated S-FLC Lambda is not in itself a diagnosis and does not automatically mean that myeloma or other plasma cell disease is present. Lambda can also be elevated in cases of impaired kidney function, inflammation, infection and other conditions with increased polyclonal immunoglobulin production.
It is primarily the combination of S-FLC Lambda, S-FLC Kappa, the kappa/lambda ratio and other clinical and laboratory findings that determine how the result should be assessed.
