Free light chains: Eclectic multipurpose biomarker

Abstract

The production of antibodies is accompanied by a slight excess of synthesis of κ and λ immunoglobulin light chains; small amounts of them are released in the peripheral blood and can also be found in various body fluids, such as synovial fluid, cerebrospinal fluid, urine and saliva. They are rapidly filtered by the glomerulus and >99% are reabsorbed from the cells of the proximal convoluted tubule, making them present in the urine in only trace amounts. The production of an excess of protein without a reason or a specific function in a biological system is rare. Free light chains, considered for years a waste product of Ig synthesis, are currently known to be very active molecules, able to bind antigens as well as whole immunoglobulin and helping to develop specific antibody affinity. The ability of free light chains to activate mast cells and then become an active part of the pathogenic mechanisms of chronic inflammatory diseases has increased interest in their clinical use, both as an attractive therapeutic target or as a biochemical marker of disease evolution or remission. This is an overview of relevant scientific interest that immunoglobulin light chains κ and λ have attracted over the years, a report on the progress in knowledge about their structure and function, with a special focus on their biological meaning and potential clinical utility in different diseases.

Dilated cardiomyopathy

“…Two important processes in heart failure are inflammation and renal impairment, both of which can increase serum immunoglobulin free light chain (FLC) κ and λ concentrations. The sum of circulating FLC κ and λ is increased in patients with autoimmune diseases 202 and DCM (A.Mat., unpublished results). A communitybased study of 15,000 individuals of the general population showed that high FLC concentration was associated with an increased risk of all-cause mortality 203 .…”

Antibody Light Chains Dictate the Specificity of Contact Hypersensitivity Effector Cell Suppression Mediated by Exosomes

“…However, currently the biological functions of LCs are being recognized. Due to their involvement in pathogenesis of various diseases, LCs are now considered as possible diagnostic markers [ 1 , 2 , 3 ]. Further, LCs play an important role in activation of mast cells and neutrophils, as well as in humoral immunity by supporting the antigen binding with sufficient affinity by specific antibodies [ 1 ].…”

“…Due to their involvement in pathogenesis of various diseases, LCs are now considered as possible diagnostic markers [ 1 , 2 , 3 ]. Further, LCs play an important role in activation of mast cells and neutrophils, as well as in humoral immunity by supporting the antigen binding with sufficient affinity by specific antibodies [ 1 ]. This is often associated with the development of various chronic inflammatory disorders and tumor-related inflammation, in which LCs seem to promote the pathological immune reactivity of particular cells [ 1 , 4 , 5 ].…”

Plasmatic free light chains as inflammatory marker in insulin resistance: comparison of metabolic syndrome with adult growth hormone deficiency

“…In recent years, FLCs have become an attractive novel target, with the aim of using antagonists to reduce inflammation and disease activity. This concept remains relatively unexplored, and further prospective studies are needed to validate the use of FLCs as a biomarker in different disease cohorts .…”

“…Immunoglobulin‐free light chains (FLCs) κ and λ are produced by plasma cells in slight excess for the need of immune response and are therefore assayable in peripheral blood, as in other biological fluids, such as urine, saliva, cerebrospinal fluid, and synovial fluid . However, recently, different biological functions have been attributed to these molecules, suggesting that they are not just a secondary product of immunoglobulin synthesis.…”