Immunoglobulin light chain amyloid fibrils (AL fibrils)

Immunoglobulin light chain amyloid fibrils are insoluble, beta-sheet rich protein aggregates derived from misfolded monoclonal immunoglobulin light chains, typically produced by clonal plasma cells (Source: Merlini et al., Nature Reviews Disease Primers, 2018). These fibrils are the primary pathogenic drivers of AL amyloidosis, a systemic disorder where the aggregates deposit in vital organs such as the heart, kidneys, and liver (Source: National Organization for Rare Disorders [NORD], 2023). The deposition leads to mechanical disruption of tissue architecture and direct proteotoxicity, which causes progressive organ dysfunction and eventual failure (Source: Gertz, American Journal of Hematology, 2022). Therapeutic strategies targeting these fibrils focus on promoting their clearance or preventing further aggregation to restore organ function. Investigational monoclonal antibodies, such as birtamimab and anselamimab, are designed to bind to cryptic epitopes on the fibrils to trigger immune-mediated removal by macrophages (Source: Prothena Corporation, 2024; Caelum Biosciences, 2024). This approach is distinct from traditional chemotherapy, which targets the underlying plasma cell clone rather than the amyloid deposits themselves.

Other names

AL amyloidAmyloid light-chain fibrilsMonoclonal light chain amyloidLight chain amyloid deposits

Monoclonal antibodies bind to specific cryptic epitopes exposed only on misfolded light chains or amyloid fibrils, facilitating immune-mediated clearance via phagocytosis and neutralizing soluble toxic aggregates (Source: Merlini et al., 2018; Prothena, 2024).