Immunoglobulin lambda light chain amyloid fibril (AL amyloid fibril)

Immunoglobulin lambda light chain amyloid fibrils are pathological protein aggregates that characterize AL amyloidosis, a systemic disorder resulting from a plasma cell dyscrasia. These fibrils are composed of misfolded monoclonal light chains, predominantly of the lambda isotype, which assemble into insoluble cross-beta sheet structures that deposit in extracellular tissues (Merlini et al., 2018, Nature Reviews Disease Primers). The accumulation of these fibrils causes mechanical disruption of tissue architecture and exerts direct proteotoxic effects, particularly on cardiomyocytes and renal cells, leading to organ failure. While traditional therapies focus on suppressing the production of precursor light chains by targeting plasma cells, the fibrils themselves have emerged as a distinct therapeutic target. Investigational monoclonal antibodies, such as anselamimab and birtamimab, are designed to bind specifically to the misfolded or fibrillar forms of the light chain to promote their clearance via antibody-dependent cellular phagocytosis (Gertz et al., 2020, Blood Cancer Journal). This targeted approach aims to accelerate organ recovery by reducing the existing amyloid burden and neutralizing toxic intermediates.

Other names

AL amyloidImmunoglobulin light chain amyloidMisfolded lambda light chainAmyloid light-chain fibril

Monoclonal antibodies target cryptic epitopes on the misfolded light chains or fibrils, inducing macrophage-mediated clearance (phagocytosis) and preventing further aggregation (Gertz et al., 2020, Blood Cancer Journal).