Immunoglobulin light chain amyloid fibril (AL fibril) (AL fibril)

Immunoglobulin light chain (AL) fibrils are insoluble, pathological protein aggregates composed of misfolded monoclonal light chains produced by clonal plasma cells [1]. These fibrils possess a characteristic cross-beta sheet structure that makes them resistant to normal proteolytic degradation, leading to their accumulation in the extracellular space of vital organs such as the heart, kidneys, and liver [3]. The deposition of AL fibrils causes mechanical disruption of tissue architecture and exerts direct proteotoxic effects, resulting in progressive organ failure and high mortality [2]. While traditional treatments focus on eliminating the underlying plasma cell clone, emerging therapies specifically target the AL fibrils to accelerate their removal and neutralize circulating toxic precursors [4]. These fibril-targeting agents, primarily monoclonal antibodies, aim to improve organ function and survival by promoting the clearance of existing amyloid deposits through immune-mediated mechanisms [2, 4].

Other names

Amyloid light-chain fibrilAL amyloidMonoclonal light chain amyloidImmunoglobulin light chain aggregate

Monoclonal antibodies bind to cryptic epitopes on misfolded light chains or the amyloid fibril surface to neutralize toxic species and stimulate macrophage-mediated clearance of tissue deposits [2, 4].