From the Guidelines
Immunoglobulin light chains are protein components of antibodies that play a crucial role in the immune system, and their levels can be measured using serum free light chain assay in patients with multiple myeloma. According to the study by 1, in patients with predominantly light chain monoclonal protein, the serum free light chain assay can be used for measurement of monoclonal kappa or lambda light chain levels.
Key Points
- Immunoglobulin light chains are essential for the formation of complete immunoglobulin molecules, working alongside heavy chains to create the characteristic Y-shaped structure of immunoglobulins.
- There are two types of light chains in humans: kappa (κ) and lambda (λ), with each person's B cells producing either one type or the other for a specific antibody.
- Light chains contain approximately 220 amino acids and include both variable and constant regions, with the variable region working with the heavy chain's variable region to form the antigen-binding site.
- In certain conditions like multiple myeloma, abnormal plasma cells may produce excess free light chains that can be detected in blood or urine, serving as important diagnostic markers for these diseases, as noted in the study by 1.
Measurement of Immunoglobulin Light Chains
- The level of monoclonal protein in the blood can be measured using serum protein electrophoresis, but in patients with certain immunoglobulins like IgA, quantitation of the immunoglobulin by nephelometry can be used instead.
- In patients with very low levels of monoclonal protein, immunofixation with isotype-specific antibodies can detect the presence of the monoclonal protein.
- The serum free light chain assay is a useful tool for measuring monoclonal kappa or lambda light chain levels in patients with predominantly light chain monoclonal protein, as stated in the study by 1.
From the Research
Definition and Biology of Immunoglobulin Light Chains
- Immunoglobulin light chains (LCs) are components of antibodies, with a free form observed in the circulation, originating from 10 to 40% excess synthesis over heavy chain in B cells 2.
- Complete antibodies function as a defined tetramer structure unit, H2L2; thus, separation of heavy and light chains results in considerable or complete loss of antigen-binding ability 2.
- Free IgLC has been considered as an inconsequential spillover during antibody assembly, but recent findings suggest that free IgLC is involved in a wide range of immunological phenomena as a signaling effector or an anti-inflammatory molecule 2.
Clinical Implications of Immunoglobulin Light Chains
- High serum levels of free clonal immunoglobulin light chains (LCs) can cause myeloma kidney (cast nephropathy), leading to severe acute kidney injury in patients with multiple myeloma 3, 4.
- Patients with light chain-predominant multiple myeloma have a significantly higher death rate, a higher rate of chronic dialysis, and a lower estimated glomerular filtration rate, associated with renal damage caused by excess free immunoglobulin light chains 4.
- The removal of free light chains by means of extracorporeal blood purification systems, such as plasma exchange or high cut-off hemodialysis, may facilitate the recovery of renal function in patients with multiple myeloma 3, 5.
Detection and Diagnosis of Immunoglobulin Light Chain-Related Diseases
- Immunohistochemistry (IHC) and in situ hybridization studies can show a mixture of kappa and lambda plasma cells, and flow cytometry can detect ambiguous results for cytoplasmic Ig light chains kappa and lambda 6.
- Double IHC can demonstrate co-expression of kappa and lambda light chains in the same cells, and fluoresces in situ hybridization studies can be positive for specific translocations, such as t(11;14)(q13;q32) 6.
- Laboratory and clinical findings, including urine protein concentration, serum albumin, and estimated glomerular filtration rate, can be used to diagnose and monitor immunoglobulin light chain-related diseases 4.