The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V-L germ line gene use and clonal plasma cell burden

Primary systemic amyloidosis (AL) is a protein conformation disorder in whi ch monoclonal immunoglobulin light chains produced by clonal plasma cells a re deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ trop ism is unknown. This study tested the hypothesis that both the light-chain variable region (Ig V-L) germ line genes used by AL clones and the plasma c ell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig V-L gene s were sequenced from 60 AL patients whose dominant involved organs were re nal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a V-lam bda VI germ line gene were more likely to present with dominant renal invol vement, whereas those with clones derived from the 1c, 2a2, and 3r V-lambda genes were more likely to present with dominant cardiac and multisystem di sease. Patients with V-kappa clones were more likely to have dominant hepat ic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac Involvement Indep endent of germ line gene use. In the In vitro model, unlike all other AL li ght chains tested, lambda VI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis tha t germ line gene use and plasma cell burden influence the organ tropism of AL. (C) 2001 by The American Society of Hematology.