Amyloid light-chain protein (AL)

Amyloid light-chain (AL) protein is a misfolded form of monoclonal immunoglobulin light chains, typically produced by an underlying plasma cell dyscrasia [StatPearls]. These proteins aggregate into insoluble fibrils that deposit in various tissues, leading to systemic AL amyloidosis, a condition characterized by progressive organ failure, particularly in the heart and kidneys [NIH]. Unlike the native light chains that function as part of the adaptive immune system, AL proteins exhibit proteotoxicity and structural instability [PubMed]. Therapeutic interventions targeting the AL protein include monoclonal antibodies that specifically recognize the misfolded conformation or amyloid fibrils [Journal of Clinical Oncology]. These agents, such as birtamimab and anselamimab, aim to accelerate the removal of existing deposits and neutralize toxic precursors, providing a direct mechanism to improve organ function alongside chemotherapy that targets the source plasma cells [Clinical Lymphoma Myeloma and Leukemia].

Other names

Immunoglobulin light chain amyloidAL amyloidMonoclonal light chainMisfolded immunoglobulin light chainAmyloidogenic light chain

Monoclonal antibodies bind to cryptic epitopes on misfolded or aggregated light chains to neutralize circulating toxic species and promote the clearance of amyloid deposits through antibody-dependent cellular phagocytosis [PubMed].