We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the λ type responsible for nonamyloid A light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical 'Randall-type' κ light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid κ deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC λ mRNAs had a normal overall structure consisting of Vλ2 segments rearranged to Jλ2Cλ2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.
ASJC Scopus subject areas
- Pathology and Forensic Medicine