Urine Immunoglobulin Light Chain Fragments Detected by MALDI-TOF Mass Spectrometry

To the Editor: Immunoglobulin light chain (LC) fragments in the urine of patients have been known for many years (1). Previously, a comparison of urine monoclonal protein (M-protein) detection between u-Mass-Fix, which uses matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and urine immunofixation electrophoresis (u-IFE) was presented (2). Unlike u-IFE where urine protein concentration removes proteins below 10 000 Daltons (Da), u-Mass-Fix is performed neat allowing lower-mass LC fragments to be detected. Mass measurement of urinary LC-fragments enables unique characterizations in comparison to enzymatic digestion and western blot methodologies. Monoclonal free LCs can cause kidney injury via epithelial cell absorption and toxicity (3–5). LC-fragments may be a byproduct of epithelial cell processing and could be a biomarker of early-onset M-protein related renal disease. Clarifying LC-fragment origin (i.e., pre-renal, renal, or post-renal) is important prior to undertaking an association study. To provide insight into urine LC-fragments, a subcohort of patients from the previous study (2) was created to include only patients with 2 or more follow-up u-Mass-Fix evaluations. In total, the subcohort contained 229 patients with plasma cell diseases (PCDs), with a median of 5 follow-up u-Mass-Fix tests over a 34-month period. All u-Mass-Fix spectra were reviewed for intact M-proteins, M-protein LC glycosylation, and LC-fragments with mass-to-charge ratios (m/z) between 4000 and 32 000 Da. LC-fragments are defined as peaks with a mass lower than an intact light chain. All peaks were detected visually, and relative peak intensities were not recorded. All LC fragments were identified after anti-kappa and anti-lambda immune- enrichment, indicating that all detected LC-fragments contained a portion of the constant region (CR).