Human immunoglobulin molecules consist of two identical heavy chains which define immunoglobulin classes (IgG, IgA, IgM, IgD and IgE) and identical light chains (kappa or lambda) that are covalently linked to a heavy chain. In healthy individuals, the majority of light chains in serum exist bound to heavy chain. However, low levels of free light chains (FLCs) are found in serum of normal individuals due to their excess production over heavy chains by mature B-cells. In serum, FLC kappa exists predominantly as a monomer with a molecular weight of 22.5 kDa and FLC lambda as a dimer with a molecular weight of 45 kDa. This size difference results in a differential glomerular filtration rate and, consequently, a ratio of FLC kappa to FLC lambda of 1:1.6 in serum.
FLCs are observed in urine too but filtration and reabsorption of low molecular proteins in the kidney strongly affects the FLC concentration so that urinary FLC level is low in healthy individuals.
FLC are a natural product of B lymphocytes and, as such, represent a unique biomarker of neoplastic and reactive B cell-related disorders. Increased FLCs are associated with malignant plasma dyscrasia and other lymphocyterelated immunoproliferative disorders.
The detection of the FLCs is important diagnostic aid for a variety of monoclonal gammopathies, such as multiple myeloma, Waldenstrom macroglobulinemia, nonsecretory myeloma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance. Accurate measurement of monoclonal free light chains in serum and/or urine is especially important in light-chain diseases, such as light-chain myeloma, primary systemic amyloidosis, and light chain-deposition disease. The ability to quantify monoclonal FLCs may be useful to monitor the disease. In patients with light chain myeloma, either of light chain, kappa or lambda, is dominantly produced and resulting in marked changes of the FLC κ/λ ratio in the early phase of the disease. The detection of urinary monoclonal kappa or lambda free light chains of immunoglobulin, also know as Bence Jones proteins (BJP), are important for identifying and monitoring Bcell malignancies too.
In addition, compared with the healthy state, the synthesis of polyclonal FLC is markedly increased in conditions associated with B cell activation as found in certain inflammatory or autoimmune diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis, as well as in cancer, diabetes mellitus, and AIDS).
- References to Immunoglobulin Free Light Chains Kappa and Lambda (FLC)