Immunoglobulin light chain amyloid fibril (AL amyloid fibril)

Immunoglobulin light chain amyloid fibrils are pathological protein aggregates formed from misfolded monoclonal immunoglobulin light chains secreted by abnormal plasma cells. In AL amyloidosis, these misfolded proteins assemble into insoluble fibrils with a cross-β sheet structure and deposit extracellularly in multiple organs, especially the heart and kidneys, leading to progressive dysfunction and high mortality. The fibril formation stems from unique patient-specific mutations, resulting in a highly heterogeneous molecular pathology. AL amyloid fibril deposition is a direct therapeutic target; existing therapies focus on eradicating the underlying plasma cell clone, thereby stopping the supply of amyloidogenic light chains, but no current drugs dissolve established fibrils. Diagnosis and therapy are challenged by disease heterogeneity, rapid progression, and potential irreversible organ injury[2][5][6][7][9][8][4][10][1][3].

Other names

AL amyloid fibrilAmyloid light chain fibrilImmunoglobulin light chain-derived amyloid fibrilAL amyloidosis fibrilPrimary systemic amyloid fibril

Plasma cell cytotoxicity (chemotherapeutics, e.g., melphalan, cyclophosphamide: kill plasma cells to lower light chain levels) Proteasome inhibition (e.g., bortezomib, ixazomib: block plasma cell protein degradation pathways) Immunomodulation (lenalidomide, pomalidomide: enhance immune clearance of plasma cells) Monoclonal antibody-mediated plasma cell depletion (daratumumab: targets CD38 on plasma cells) Indirect: Reduction of precursor proteins — lowering light chain supply prevents further fibril growth