What is S-FLC Kappa?
S-FLC Kappa is a biomarker that measures the concentration of free immunoglobulin light chains of the kappa type in serum. Kappa chains are part of immunoglobulins, i.e. antibodies produced by B lymphocytes and plasma cells.
Each immunoglobulin consists 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 into complete immunoglobulins. These circulate freely in the blood and are called free light chains, or FLC.
What function do free kappa chains have?
Free kappa chains have no separate hormonal or enzymatic function, but arise as a natural part of immunoglobulin production. They are continuously formed by plasma cells and are eliminated mainly via the kidneys.
The level of free kappa chains in the blood is therefore affected both by how much immunoglobulin is produced and by the kidneys' ability to eliminate the free chains.
Why is S-FLC Kappa analyzed?
S-FLC Kappa is primarily analyzed together with S-FLC Lambda and when investigating suspected monoclonal immunoglobulin production.
The analysis is used, among other things, as a complement in the investigation and follow-up of conditions in which a group of plasma cells produces a larger amount of a certain type of immunoglobulin or free light chain. Examples include:
- MGUS, monoclonal gammopathy of undetermined significance
- multiple myeloma
- light chain myeloma
- AL amyloidosis
- other plasma cell and immunoglobulin-related diseases
S-FLC can complement serum protein fractions and immunofixation because free light chains are sometimes present in amounts that are not captured as clearly with traditional serum protein analysis alone.
How is an elevated S-FLC Kappa interpreted?
An elevated value of free kappa chains means that the concentration of free kappa chains in serum is higher than expected. Such a finding always needs to be assessed together with the level of free lambda chains and the kappa/lambda ratio.
If both kappa and lambda are elevated and the ratio is still within or close to the reference range, it may indicate a more general, polyclonal increase in immunoglobulin production. This can be seen in, for example, inflammation, infection, autoimmune disease or impaired renal function.
However, if the kappa chains are clearly elevated at the same time as the kappa/lambda ratio is pathologically shifted towards kappa, this may indicate a monoclonal production of free kappa chains. Such a finding may occur in, for example, MGUS, myeloma or other plasma cell diseases and needs to be assessed together with other laboratory and clinical findings.
Why is the kappa/lambda ratio important?
The absolute kappa value cannot be interpreted in isolation. Since both kappa and lambda can increase simultaneously in, for example, impaired kidney function or general activation of the immune system, the relationship between the two chains is often more diagnostically informative.
describes the balance between free kappa chains and free lambda chains. A clearly deviating ratio may indicate that a plasma cell clone produces a disproportionate amount of one type of light chain.
In kappa excess, the kappa/lambda ratio is elevated, while lambda excess results in a lowered ratio. A significantly deviating ratio may give a stronger suspicion of monoclonal light chain production than an isolated elevated kappa or lambda value.
How does kidney function affect S-FLC Kappa?
Free light chains are eliminated mainly via the kidneys. In cases of impaired kidney function, both kappa and lambda can accumulate in the blood and give elevated concentrations without the need for a monoclonal plasma cell disease.
When interpreting S-FLC Kappa, it is therefore important to consider kidney function, such as creatinine and eGFR. Reference intervals and interpretation of the kappa/lambda ratio may also need to be adjusted in cases of pronounced renal impairment.
What does a low S-FLC Kappa mean?
A low value of free kappa chains is usually of less clinical significance than an elevated value or an abnormal kappa/lambda ratio. A low kappa value can occur with low immunoglobulin production or immunosuppression, but needs to be assessed in relation to lambda chains, total immunoglobulins and other clinical findings.
S-FLC Kappa together with Lambda and the ratio
S-FLC Kappa should not be assessed as a standalone biomarker in practice. The clinical information becomes significantly greater when kappa is analyzed together with S-FLC Lambda and .
The Free immunoglobulin chains (FLC) blood sample analyzes all three components. The results show both the absolute levels of kappa and lambda and the balance between them, which allows for a better distinction between polyclonal changes and possible monoclonal production.
What other analyses are assessed together with S-FLC Kappa?
If monoclonal gammopathy is suspected, S-FLC is usually assessed together with other analyses, for example:
- serum protein fractions or serum eluphoresis
- immunofixation
- immunoglobulins IgG, IgA and IgM
- hemoglobin and other blood status
- creatinine and eGFR
- calcium
If AL amyloidosis or certain other plasma cell diseases are suspected, additional serum and urine analyses may be needed.
Analysis method
S-FLC Kappa is analyzed using an immunochemical method, usually nephelometry. The method measures the concentration of free kappa chains in serum and the result is usually given in mg/L.
Reference range
The reference range varies between laboratories and analysis methods. Karolinska University Hospital specifies a reference range for S-Kappa chain, free of 6.7–22.4 mg/L for its method. The reference range stated on the current laboratory result should always be used when interpreting.
Important to know
An elevated S-FLC Kappa is not in itself a diagnosis and does not automatically mean that myeloma or other malignant plasma cell disease is present. Elevated levels can also be seen in inflammation, infection, autoimmune disease and impaired kidney function.
It is primarily the combination of free kappa chains, free lambda chains, the kappa/lambda ratio and other laboratory findings that determine how the result should be assessed. In the event of clearly deviating values or pathological ratios, further medical investigation may be warranted.
