Monitoring free light chains in serum using mass spectrometry

David R. Barnidge, Angela Dispenzieri, Giampaolo Merlini, Jerry A. Katzmann, David L. Murray

Research output: Contribution to journalArticle

Abstract

Background: Serum immunoglobulin free light chains (FLC) are secreted into circulation by plasma cells as a by-product of immunoglobulin production. In a healthy individual the population of FLC is polyclonal as no single cell is secreting more FLC than the total immunoglobulin secreting cell population. In a person with a plasma cell dyscrasia, such as multiple myeloma (MM) or light chain amyloidosis (AL), a clonal population of plasma cells secretes a monoclonal light chain at a concentration above the normal polyclonal background. Methods: We recently showed that monoclonal immunoglobulin rapid accurate mass measurement (miRAMM) can be used to identify and quantify a monoclonal light chain (LC) in serum and urine above the polyclonal background. This was accomplished by reducing immunoglobulin disulfide bonds releasing the LC to be analyzed by microLC-ESI-Q-TOF mass spectrometry. Here we demonstrate that the methodology can also be applied to the detection and quantification of FLC by analyzing a non-reduced sample. Results: Proof of concept experiments were performed using purified FLC spiked into normal serum to assess linearity and precision. In addition, a cohort of 27 patients with AL was analyzed and miRAMM was able to detect a monoclonal FLC in 23 of the 27 patients that had abnormal FLC values by immunonephelometry. Conclusions: The high resolution and high mass measurement accuracy provided by the mass spectrometry based methodology eliminates the need for κ/λ ratios as the method can quantitatively monitor the abundance of the κ and λ polyclonal background at the same time it measures the monoclonal FLC.

Original languageEnglish
Pages (from-to)1073-1083
Number of pages11
JournalClinical Chemistry and Laboratory Medicine
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Keywords

  • free light chains
  • mass spectrometry
  • microflow LC-ESI-Q-TOF MS
  • monoclonal
  • κ
  • λ

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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