Immunoglobulin light chain (FLC) (FLC)

Immunoglobulin light chains are small protein subunits, existing as either kappa or lambda types, produced by plasma cells as part of the adaptive immune system (Merlini et al., 2018, Nature Reviews Disease Primers). In systemic light-chain (AL) amyloidosis, a clonal population of plasma cells overproduces monoclonal free light chains that are prone to misfolding (Gertz et al., 2020, American Journal of Hematology). These misfolded proteins aggregate into insoluble amyloid fibrils that deposit in vital organs such as the heart, kidneys, and liver, causing progressive damage (Palladini et al., 2020, Blood). The accumulation of these fibrils leads to organ failure through both mechanical disruption of tissue architecture and direct proteotoxicity to cells like cardiomyocytes (Merlini et al., 2018). Therapeutic strategies targeting these light chains involve monoclonal antibodies designed to bind specifically to misfolded or aggregated forms, facilitating their clearance by the immune system (Gertz et al., 2023, Blood). Drugs such as birtamimab and anselamimab recognize cryptic epitopes exposed only on amyloidogenic light chains, promoting macrophage-mediated phagocytosis (Edwards et al., 2021, Amyloid). This approach aims to neutralize toxic intermediates and remove existing deposits, complementing chemotherapy which stops the production of new light chains (Sanchorawala et al., 2023, Journal of Clinical Oncology).

Other names

Monoclonal free light chainAmyloidogenic light chainBence-Jones proteinAL proteinImmunoglobulin kappa light chainImmunoglobulin lambda light chain

Monoclonal antibodies bind to cryptic epitopes on misfolded light chains and amyloid fibrils to facilitate immune-mediated clearance via phagocytosis and neutralize proteotoxic species (Gertz et al., 2023; Edwards et al., 2021).