Human Immunoglobulin Free Light Chains Kappa and Lambda ELISA Kit

The basic structure of antibodies is composed of two identical heavy chains (H chains) and two identical light chains (L chains) connected by interchain disulfide bonds, forming a "Y"-shaped tetrapeptide chain molecule. The amino acid composition of the two H chains and two L chains in a natural Ig molecule is exactly the same. The relative molecular mass of the immunoglobulin heavy chain is 50,000 to 75,000, and it is composed of 450 to 550 amino acid residues. According to the differences in heavy chain structure and antigenicity, it can be divided into 5 categories: μ chain, γ chain, α chain, δ chain and ε chain; immunoglobulins composed of different heavy chains and light chains are called IgM, IgG, IgA, IgD and IgE respectively. The same class of Ig has different amino acid compositions in the hinge region and the number and position of heavy chain disulfide bonds, and the same class of Ig can be divided into different subclasses based on this. For example, human IgG can be divided into IgG1 to IgG4; IgA can be divided into IgA1 and IgA2. IgM, IgD and IgE have not yet been found to have subclasses. The relative molecular mass of immunoglobulin light chain is about 25,000, and it is composed of 211 to 219 amino acid residues. According to the difference in light chain structure and antigenicity, it is divided into κ (kappa) chain and λ (lambda) chain, and Ig can be divided into two types, namely κ type and λ type. The types of the two light chains on a natural immunoglobulin molecule are always the same, but immunoglobulin molecules with κ or λ chains can exist in the same body, and there is no difference in the functions of the two types of light chains. The ratio of the two types of light chains in different species is different. The normal human serum immunoglobulin κ:λ is about 2:1, while in mice it is 20:1. Abnormal κ:λ ratio may reflect abnormalities in the immune system. For example, if there are too many λ chains in human immunoglobulins, it indicates that there may be B cell tumors that produce λ chains. According to the differences in individual amino acids in the constant region of the λ chain, it can be divided into four subtypes from λ1 to λ4.

Figure 1. Structure of a normal immunoglobulin (Ig) molecule.(Sources: Oruba Z, et al. 2018)

Light chains (L) usually do not contain carbohydrates and have a molecular weight of about 24kD. Each light chain contains two cyclic peptides composed of intrachain disulfide bonds. Light chains are small molecular proteins that can freely pass through the glomerular basement membrane and are reabsorbed back into the blood circulation in the renal tubules, so only a small amount of light chains exist in normal human urine. The half-life of normal human light chains is 4 hours, and that of patients with renal dysfunction is 8 to 32 hours. When metabolic disorders and multiple myeloma occur, a large amount of free light chains appear in the blood and are excreted in the urine, which is Bence-Jones protein. Light chain disease is most closely related to multiple myeloma. About 20% of myeloma patients only secrete free light chains, and about 50% of myeloma patients have both monoclonal serum immunoglobulins and monoclonal urine light chains. The former has a poor prognosis. Light chains are mostly of the λ type, and their prognosis is worse than that of the κ chain type. The concentration of light chains in blood and urine is related to the number of monoclonal cells that produce light chains, the synthesis rate, and renal function. However, for the same patient, the protein synthesis rate of light chain-secreting cells usually remains unchanged. Under normal renal function conditions, the quantitative determination of urinary light chains is of reference value for the diagnosis, staging, and prognosis of myeloma.

The detection of light chains and serum free light chains (sFLC) is mainly used to diagnose plasma cell diseases (PCD), including the above-mentioned multiple myeloma (MM), primary amyloidosis, monoclonal gammopathy, and primary macroglobulinemia. In these diseases, a single (monoclonal) plasma cell overproliferates and produces a large number of abnormal antibodies, which in turn affects the content of LC & sFLC and the κ/λ ratio, so it can be used as an important indicator for detecting plasma cell diseases. Compared with serum total light chains (sTLC), the content of serum free light chains (sFLC) in the human body is less, which can more sensitively reflect the abnormal concentration. In addition, the detection site of the sTLC reagent is the exposed site on the outside where the light chain binds to the heavy chain, while the sFLC detects the hidden site on the inside of the light chain, which can only be detected when the light chain is free. If sTLC is detected alone, misdiagnosis and missed diagnosis are very likely to occur. Therefore, sFLC has become a marker superior to sTLC determination in recent years. Currently, many authoritative guidelines have pointed out the important role of sFLC detection in the diagnosis and prognosis evaluation of various plasma cell diseases, especially MM.

Lambda Light Chain
λ Light Chain
Immunoglobulin Lambda Chain
IgLλ
Lambda Chain Immunoglobulin