Antibodies gone bad - the molecular mechanism of light chain amyloidosis

Light chain amyloidosis (AL) is a systemic disease in which abnormally proliferating plasma cells secrete large amounts of mutated antibody light chains (LCs) that eventually form fibrils. The fibrils are deposited in various organs, most often in the heart and kidney, and impair their function. The prognosis for patients diagnosed with AL is generally poor. The disease is set apart from other amyloidoses by the huge number of patient-specific mutations in the disease-causing and fibril-forming protein. The molecular mechanisms that drive the aggregation of mutated LCs into fibrils have been enigmatic, which hindered the development of efficient diagnostics and therapies. In this review, we summarize our current knowledge on AL amyloidosis and discuss open issues.

Automated summary

Light chain amyloidosis (AL) is a systemic disease characterized by abnormal proliferation of plasma cells and the secretion of mutated antibody light chains (LCs) that form fibrils. These fibrils deposit in various organs, particularly the heart and kidney, impairing their function. The molecular mechanisms underlying the aggregation of mutated LCs into fibrils remain unclear, hindering the development of effective diagnostics and therapies.