The V kappa III subgroup light chain proteins in AL amyloidosis & autoimmune diseases

Background & objectives: Light chain associated amyloidosis (AL) is charact erized by extracellular deposition of immunoglobulin tight chain and its fr agments. fn vitro and in vivo studies have shown that some light chains are nonamyloidogenic and nonnephrotoxic, whereas others are potentially amyloi dogenic. Some light chains are prone to be deposited as rheumatoid material s, and also as nodular amorphous aggregates (tight chain deposition disease s). These findings suggest that specific sequence element(s) may control th e various hinds of light chain associated diseases. In this study we tried to identify such sequence element(s). Methods: Two Bence Jones proteins (BJPs), NIG93 and NIG2 of subgroup V kapp a III, were characterized and compared with other members of the same subgr oup whose sequences are available in the data base. Results: Both NIG93 and NIG2 proteins Iliad sequences characteristics of V kappa Illa as distinguished from V kappa IIIb, subsubgroup proteins. They a lso contained several novel substitutions, such as Met-37, Leu-40, Val-58, and Ile-85 in NIG93, and Val-2, His-29, Arg-50, and Ile-72 in NIG2. The dat a accumulated at present indicate that alt members of the V kappa IIIa subs ubgroup are related to either AL amyloidosis or rheumatoid arthritis, where as the V kappa IIIb proteins are related to autoimmune diseases, Interpretation & conclusion: These observations indicate that subgroup-spec ific residues might be critical for light chain pathogenesis, at least for the Will proteins. Point mutations within these proteins may be another str uctural element controlling their conformation as well as their pathogenic aggregation.