Serum Free Light Chain Analysis

In healthy individuals, plasma cells originating from the bone marrow produce immunoglobulin molecules composed of two heavy chains and two light chains. There are two types of light chains in humans. The κ light chains are encoded by the immunoglobulin κ locus on chromosome 2 and λ light chains are encoded by the immunoglobulin λ locus on chromosome 22 [1]. During B lymphocyte development, the light chains that are produced bind to heavy chains via interchain disulfide bonds and noncovalent interactions to form intact immunoglobulin molecules. However, light chains are usually produced in excess (up to 40 %) and those that do not bind to heavy chains enter the bloodstream as serum free light chains (sFLCs)[2]. The low molecular weight of the sFLCs (κ monomers: 22.5 kDa, λ dimers: 45 kDa) allows them to be filtered freely through the glomeruli. They are then almost completely reabsorbed in the proximal tubules via the megalin/cubulin scavenger receptors [3]. Trace amounts of immunoglobulins are secreted into the distal nephron and urethra along with secretory IgA as a mucosal defense mechanism, which may explain the 1–10 mg/24 h of FLCs found in the urine of normal individuals [4]. In plasma cell dyscrasias, such as in multiple myeloma (MM), the abnormally expanded clone of malignant plasma cells produces an excess of monoclonal immunoglobulins that are referred to as M-proteins or paraproteins. These M-proteins may be polymers, monomers, individual immunoglobulin chains of FLCs or heavy chains, or fragments of immunoglobulins. Very rarely occurring is the nonsecretory