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Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma [36] [37] [38] and chronic lymphocytic leukaemia. [39] An abnormal light-chain ratio has been defined as a kappa to lambda chain ratio of less than 0.26 or more than 1.65. [32]
Once set, light chain class remains fixed for the life of the B lymphocyte. In a healthy individual, the total kappa-to-lambda ratio is roughly 2:1 in serum (measuring intact whole antibodies) or 1:1.5 if measuring free light chains, with a highly divergent ratio indicative of neoplasm. The free light chain ratio ranges from 0.26 to 1.65. [1]
It is important in quantification of free light chains in diseases such as multiple myeloma. Quantification is important for disease classification and for disease monitoring once a patient has been treated (increased skewing of the ratio between kappa and lambda light chains after a patient has been treated is an indication of disease recurrence).
The variable region of light is therefore encoded by the rearrangement of VJ segments. The light chain can be either kappa,κ or lambda,λ. This process takes place at the level of mRNAs processing. Random rearrangements and recombinations of the gene segments at DNA level to form one kappa or lambda light chain occurs in an orderly fashion.
These chains are usually present in a 70:30 ratio of kappa to lambda. Anti-lambda light chain antibodies can nonspecifically bind to multiple isotypes of immunoglobulins. [22] Immunoglobulins will either express Kappa or Lambda light chains. This is a depiction of an immunoglobulin that expresses Lambda light chains.
[70] [79] These biomarkers are >60% clonal plasma cells, a serum involved / uninvolved free light chain ratio ≥ 100 (the concentration of the involved free light chain must be ≥ 100 mg/L) and more than one focal lesion ≥ 5 mm by MRI. [70] [79] Together, these biomarkers and the CRAB criteria are known as myeloma-defining events (MDEs).
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The remainder get solutions with anti-IgG, anti-IgA, anti-IgM, anti-kappa light chain and anti-lambda light chain immunoglobulin, respectively from left to right. Each anti-immunoglobulin solution is artificially colored to ensure that the solution matches the color map at top. Immunofixation electrophoresis, schematic representation: