Misfolded immunoglobulin light chain amyloid aggregate (AL amyloid) (AL amyloid)

Misfolded immunoglobulin light chain amyloid aggregates are the primary pathogenic drivers of AL amyloidosis, a systemic disease characterized by the deposition of insoluble protein fibrils in vital organs (Merlini et al., 2011). These aggregates arise from the clonal production of unstable monoclonal light chains by plasma cells, which undergo a conformational shift to form beta-sheet rich fibrils (Sipe et al., 2016). The accumulation of these fibrils in tissues such as the heart, kidneys, and liver leads to progressive organ failure and significant morbidity. Therapeutic interventions targeting these aggregates, such as monoclonal antibodies like birtamimab and anselamimab, aim to recognize specific neoepitopes exposed during misfolding to facilitate the removal of existing deposits and neutralize toxic intermediates (Edwards et al., 2021). This approach complements traditional plasma cell-directed therapies by directly addressing the tissue-resident amyloid burden.

Other names

AL amyloid fibrilLight chain amyloidImmunoglobulin light chain amyloidAL fibrilAmyloid light-chain aggregate

Monoclonal antibodies target cryptic epitopes or neoepitopes exposed only on misfolded or aggregated light chains. This binding facilitates the clearance of amyloid deposits via antibody-dependent cellular phagocytosis (ADCP) by macrophages and neutralizes the toxic effects of soluble misfolded light chain species (Sanchorawala et al., 2023; Edwards et al., 2021).