Immunoglobulin lambda light chain fibrils (AL fibrils)

Immunoglobulin lambda light chain fibrils are pathological protein aggregates composed of misfolded monoclonal lambda light chains, which are produced by clonal plasma cells in the bone marrow (Merlini et al., 2011, Nature Reviews Disease Primers). These fibrils are the primary pathogenic agents in AL amyloidosis, a systemic disorder where the aggregates deposit in the extracellular space of vital organs, most notably the heart, kidneys, and liver (Gertz et al., 2020, JACC). The deposition leads to mechanical disruption of tissue architecture and direct proteotoxicity, eventually resulting in progressive organ failure. While native light chains are essential components of the immune system's antibody repertoire, the fibrillar form adopts a stable, insoluble cross-beta sheet conformation that is highly resistant to endogenous proteolysis (Wall et al., 2010, Amyloid). Therapeutic strategies targeting these fibrils utilize monoclonal antibodies, such as birtamimab and anselamimab, which are designed to bind specifically to epitopes that are hidden in the native protein but exposed upon misfolding (Edwards et al., 2021, Blood). These agents aim to accelerate the clearance of existing amyloid deposits through macrophage-mediated phagocytosis and to neutralize toxic oligomeric precursors, thereby facilitating organ recovery and improving patient survival.

Other names

Amyloid light chain fibrilsLambda-type amyloid fibrilsAL amyloidMisfolded immunoglobulin lambda light chainsLambda-LC fibrils

Monoclonal antibodies target cryptic epitopes exposed only on misfolded or fibrillar light chains to induce antibody-dependent cellular phagocytosis (ADCP) by macrophages and neutralize circulating toxic soluble aggregates.