Expert opinion: Serum free light chain (FLC) has the following advantages: 1. During chemotherapy for myeloma, a negative immunofixation electrophoresis is used as a criterion for complete remission; while serum free light chain can better reflect the depth of remission than immunofixation electrophoresis. Patients with negative free light chain after treatment have a longer survival than those with negative immunofixed electrophoresis (but positive free light chain); 4. Serum free light chain has a unique and irreplaceable value in the management of IgD, light chain, non-secretory myeloma and amyloidosis; it can be used as an indicator of renal function in these patients; 5. as an important criterion to determine benign and malignant plasma cell disease. As this index is relatively new, there is no national fee standard, and it is currently measured nationally at Esther for 490 RMB, which is a self-pay item. Serum free light chain assay and its clinical application Abstract: The monoclonal free light chain (FLC) assay is an important adjunctive diagnostic method for many plasma cell diseases (e.g. multiple myeloma, primary systemic amyloidosis, monoclonal gammopathy of undetermined significance, macroglobulinemia, etc.). It is an important diagnostic and monitoring tumor marker especially in patients with multiple myeloma. The existing methods for the identification and quantification of monoclonal immunoglobulins such as protein electrophoresis and immunofixation electrophoresis are not sensitive to the identification and quantification of free light chains. The serum free light chain assay [1] is a recently applied method for automated quantification of free light chains in blood with high sensitivity and good specificity. Combined application of conventional M protein identification methods can improve the early diagnosis of many malignant plasma cell diseases; in terms of monitoring, serum free light chain assay can respond to treatment and disease recurrence earlier than other indicators. It also provides very meaningful prognostic information in patients with MGUS. Keywords: free light chain, periplasmic protein, protein electrophoresis, immunofixation electrophoresis, Serum free light chain assay and their clinical application Abstract: Detection of monoclonal free light chains (FLC) is important for diagnosis and monitoring of plasma cell dyscrasias ( such as multiple myeloma, primary systemic amyloidosis (AL), monoclonal gammopathy In MM patients, FLC is an important tumor marker for diagnosis and monitoring. Current methods for detection and quantification of monoclonal proteins, such as protein electrophoresis (PE) and immunofixation Current methods for detection and quantification of monoclonal proteins, such as protein electrophoresis (PE) and immunofixation( IFE), are insensitive for detection and quantification FLCs compared with FLC immunoassay. It will improve the screening protocols’ sensitivity for many plasm cell dyscrasias , It will improve the screening protocols’ sensitivity for many plasm cell dyscrasias , and when monitoring , FLC assays can reveal responses to treatment and relapse more rapidly than other assays. Keywords: Free Light Chain (FLC) Bence Jones protein Protein Electrophoresis (PE) Immunofixation Electrophoresis (IFE) The monoclonal immunoglobulin free light chain (FLC) was originally discovered 150 years ago in the urine of myeloma patients and was defined as periplasmic protein, it is an important tumor marker [2],a homogeneous κ or λ free molecule produced by the uncontrolled proliferation of monoclonal malignant plasma cells. It appears in the serum and urine of patients with many malignant plasma cell diseases, including multiple myeloma, primary systemic amyloidosis (AL), primary macroglobulinemia, and light chain deposition disease. Urinary FLC is usually measured qualitatively and quantitatively to determine the disease status. Since the concentration of urinary FLC is largely influenced by the reabsorption capacity of the renal tubules, it cannot accurately reflect the patient’s disease status, and is therefore not the ideal choice. Recently, kits for serum free light chain quantification have been commercialized and used in many countries, and were included in the guidelines for the diagnosis and treatment of multiple myeloma and AL in 2006. In this paper, the metabolism of FLC in normal human, serum free light chain assay and clinical applications are reviewed as follows: Physiology of serum free light chain metabolism Immunoglobulins are synthesized by plasma cells and are tetramers consisting of two identical heavy chains and two identical light chains. IgD, IgE, κ and λ light chains, and each immunoglobulin either contains κ light chain or λ light chain. Human plasma cells that produce κ light chains are approximately twice as numerous as those that produce λ light chains. The polypeptide chain of each light chain contains about 220 amino acids, which fold to form a constant region and a variable region. The yield of free light chains is about 40% more than that of heavy chains, which is required for the synthesis of the proper conformation of the intact immunoglobulin molecule. Immunoglobulin light chains that are not bound into the tetrameric form are secreted in the free form. These free light chains can exist as monomers (22C27 kDa) or can be covalently or non-covalently bound into dimers (44C55 kDa) . In normal humans, plasma cells synthesize immunoglobulins with a large number of FLC molecules produced and distributed intravascularly and intervascularly. The remaining FLC is cleared by glomerular filtration, after which FLC is taken up and broken down by proximal tubular cells. Studies have shown that a large amount of FLC is reabsorbed by the kidneys daily (10-30 g/day) [8]. Normal individuals can excrete 1-10 mg per day of free light chain into the urine, along with secretory IgA and other immunoglobulins [6]. When malignant plasma cell disease occurs, monoclonal plasma cells proliferate and produce large amounts of homogeneous monoclonal free κ or λ light chain molecules that are filtered by the glomerulus. When the filtered FLC exceeds the catabolic and reabsorptive capacity of the proximal tubule, it is excreted from the urine or reaches the ascending branches of the medullary collaterals to precipitate with Tamm-Horsfall protein in a tubular fashion, often resulting in myeloma nephropathy [9]. In adults there are 1.3 million kidney units in one side of the kidney. The glomerular basement membrane restricts filtration by changing the size of the pores and molecules with molecular weights between 30 kda and 60 kda can pass freely. This results in different clearance rates for κ-monomer and λ-dimer molecules in general. κ-monomer (25 kda) has a clearance time of about 2-4 hours due to its small individual size, while λ-type FLC has a clearance time of 3-6 hours because it is often in the dimeric (45 kda) form. Therefore, the κ monomer filtration rate is approximately more than three times faster than the λ dimer, and under normal conditions the free λ concentration in serum is much higher than the κ concentration despite the higher yield of κ than λ. In an experiment investigating the passage of dextran through the capillary barrier it was shown that the clearance of a molecule with a molecular weight of 20 Kda was more than 3.2 times that of a 37 Kda molecule, and the results of Bradwell et al. showed a κ/λ clearance of 3 ([κ urine] / [λ urine] ÷ [κ serum] / [λ serum]) Although the molecular weights of polysaccharides and globulins with the same structures are different, the different κ and λ filtration rates are one reason for the lower κ than λ in serum.