Antibody-mediated resolution of light chain-associated amyloid deposits

Primary light-chain-associated (AL) amyloidosis is characterized by the dep osition in tissue of monoclonal light chains as fibrils. With rare exceptio n, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can e ffect amyloid removal, we developed an experimental model in which mice wer e injected with amyloid proteins extracted from the spleens or livers of pa tients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections of an anti-light-chain monoclonal antibody having specificity for an amyloid-rela ted epitope. The reactivity of this monoclonal antibody was not dependent o n the V-L or C-L isotype of the fibril, but rather seemed to be directed to ward a P-pleated sheet conformational epitope expressed by AL and other amy loid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved ops onization of fibrils by the antibody, leading to cellular activation and re lease of proteolytic factors. The demonstration that AI. amyloid resolution can be induced by passive administration of an amyloid-reactive antibody h as potential clinical benefit In the treatment of patients with primary amy loidosis and other acquired or inherited amyloid-associated disorders.