Amyloid light chain (AL) protein (AL)

Amyloid light chain (AL) protein refers to the misfolded and aggregated forms of monoclonal immunoglobulin kappa (κ) or lambda (λ) light chains produced by clonal plasma cells. In AL amyloidosis, these proteins undergo a conformational change into insoluble amyloid fibrils that deposit extracellularly in vital organs such as the heart, kidneys, and liver (Merlini et al., 2018, Nature Reviews Disease Primers). This deposition causes mechanical disruption of tissue architecture and direct proteotoxicity, leading to progressive organ failure and high mortality. Therapeutic intervention focuses on neutralizing the toxic soluble aggregates and promoting the clearance of existing fibrillar deposits. Modern drug development has produced monoclonal antibodies that specifically target cryptic epitopes on the misfolded light chains, facilitating their removal by the immune system without interfering with normally folded immunoglobulins (Gertz et al., 2019, Blood). These therapies aim to improve organ function and overall survival in patients with systemic light chain amyloidosis.

Other names

Immunoglobulin light chain amyloidAL amyloidMisfolded light chainsMonoclonal light chain aggregatesKappa light chain amyloidLambda light chain amyloid

Monoclonal antibodies target cryptic epitopes exposed only on misfolded or aggregated light chains, facilitating their clearance via macrophage-mediated phagocytosis and preventing further tissue deposition (Gertz et al., 2019, Blood; Edwards et al., 2021, Amyloid).