ABSTRACT
Primary amyloidosis (AL) is a disorder characterized by overproduction and tissue deposition of monoclonal immunoglobulin (Ig) light chain (LC) fragments as insoluble amyloid fibrils, which leads to progressive organ failure. Small numbers of monoclonal bone marrow plasma cells are responsible for the secretion of amyloidogenic LCs. Analysis of somatic mutations in amyloidogenic variable region (VL) regions can provide insights into the role of antigen for the selection and clonal outgrowth of clonal amyloidogenic lymphoid cells. Ig VL gene usage in our AL patients was markedly different from the normal repertoire, with overrepresentation of a small number of germline genes, specifically 1c and 6a. The type and distribution pattern of somatic mutations were used to assess antigen selective pressure on amyloidogenic VL genes.
