Characterization of an N-linked Glycosylated Kappa Urinary Light Chain from a Patient with Primary Systemic Amyloidosis

摘要

Primary systemic amyloidosis is a protein misfolding disorder associated with extracellular deposition of immunoglobulin light chains that are overproduced by a monoclonal population of plasma cells in the bone marrow. While many previous studies have been conducted to investigate the influence of amino acid variations in the light chain variable domain on fibril formation, certain post-translational modifications (PTMs), such as glycosylation and proteolysis, may play a key role as well in rendering particular light chains amyloidogenic. In this study, we employed a mass spectrometry based method to investigate the amino acid sequence of a glycosylated kappa I light chain isolated from the urine of a patient (AL-98002) diagnosed with primary amyloidosis and to determine the glycosylation profile and other PTMs of this protein.