Human amyloid light-chain fibrils (AL fibrils)

Human AL amyloid light-chain fibrils are insoluble, pathological protein aggregates composed of misfolded monoclonal immunoglobulin light chains (kappa or lambda) produced by clonal plasma cells. These fibrils deposit in the extracellular space of vital organs, including the heart, kidneys, liver, and peripheral nerves, leading to progressive structural damage and organ failure. The fibrillar structure is characterized by a cross-beta sheet conformation that is resistant to normal proteolytic degradation. While traditional therapies focus on eliminating the underlying plasma cell clone via chemotherapy, the fibrils themselves are the target of emerging immunotherapies. These therapeutic antibodies are designed to specifically recognize and bind to the misfolded proteins, facilitating their clearance by the immune system and potentially reversing organ dysfunction in patients with systemic AL amyloidosis.

Other names

Immunoglobulin light chain amyloid fibrilsAL amyloidPrimary amyloidosis fibrilsMisfolded immunoglobulin light chains

Monoclonal antibodies bind to cryptic epitopes exposed only on misfolded light chains or fibrils, promoting clearance via antibody-dependent cellular phagocytosis (ADCP) by macrophages and neutralizing toxic soluble aggregates to prevent further deposition.