Immunoglobulin light chain amyloid deposits (AL amyloid)

AL amyloid deposits are insoluble, pathological protein aggregates composed of misfolded monoclonal immunoglobulin light chains, typically produced by a clonal population of plasma cells in the bone marrow (Merlini et al., 2018). These deposits accumulate in the extracellular space of various organs, most critically the heart and kidneys, where they disrupt tissue architecture and exert direct proteotoxic effects, leading to progressive organ failure (Gertz et al., 2020). Unlike the soluble precursor light chains, AL amyloid fibrils adopt a stable cross-beta sheet conformation that is highly resistant to endogenous clearance mechanisms. Therapeutic targeting of these deposits involves the use of specialized monoclonal antibodies, such as birtamimab and anselamimab, which are designed to recognize cryptic epitopes exposed only on the misfolded or fibrillar forms of the protein (Sanchorawala et al., 2023). By opsonizing the deposits, these drugs facilitate their removal by macrophages, aiming to reduce the total amyloid burden and promote functional organ recovery in patients with systemic AL amyloidosis (Khouri et al., 2021).

Other names

AL fibrilsAmyloid light-chain depositsPrimary amyloidosis depositsMisfolded immunoglobulin light chains

Passive immunotherapy using monoclonal antibodies that bind to neoepitopes on misfolded light chains and amyloid fibrils, promoting their clearance via macrophage-mediated phagocytosis and inhibiting further fibril growth (Khouri et al., 2021; Sanchorawala et al., 2023).