Primary structure of a variable region of the VκI subgroup (ISE) in light chain deposition disease

Abstract

SUMMARY Although structural abnormalities of monoclonal immunoglobulin light chains (LC) are suspected to play a determinant role in non-amyloid light chain deposition disease (LCDD), this condition is as yet poorly documented at the molecular level, since only three sequences have been reported to date. In a case of myeloma-associated LCDD, the patient's urine contained an unglycosylated κ Bence Jones protein made up of dimers and monomers with an apparent molecular mass of 25000 which was assigned to the VκI subgroup by N-terminal amino acid sequencing. The complete variable region sequence of the monoclonal κ chain produced by the malignant plasma cells was amplified by polymerase chain reaction (PCR) using small amounts of material obtained by bone marrow aspiration. The sequence of three independently amplified cDNA clones derived from a normal-sized κ messenger RNA was identical to that of the urinary κ chain. The κ mRNA had an overall normal structure made up of a VκI sequence rearranged to JκI- Several unusual features of the variable region (the first complete VκI sequence reported in LCDD) included three substitutions that introduced hydrophobic residues at spatially close positions. The strategy associating N-terminal sequence determination and cDNA cloning by PCR could help in accumulating new sequence data and improving our understanding of LCDD pathogenesis.