New monoclonal antibodies detect all immunoglobulin free light chains in urine samples from over 13,000 patients

J. Campbell, J. Heaney, Y. Wang, M. Cobbold, M. Goodall, T. Plant, M. Drayson

Research output: Contribution to journalMeeting abstract

Abstract

A decade or so ago, the first automated assay was launched for the quantitation of serum κ and λ immunoglobulin free light chains (FLC). FLC measurement is now a fundamental procedure in the diagnosis and monitoring of patients with plasma cell dyscrasias including multiple myeloma and related subtypes including lightchain- only, oligosecretory and non-secretory myeloma. Despite these advances, the assay, which uses sheep polyclonal anti-human FLC antibodies, has a number of well-observed limitations. It has been proposed that monoclonal antibodies (mAbs) may overcome these limitations. The development of FLC specific mAbs is difficult because the mAbs must demonstrate specificity for epitopes that are exposed on FLC but hidden on LC bound to whole immunoglobulin. This is complicated by the paucity of constant domain epitopes available; which can be further reduced by polymerisation of FLC, particularly FLC λ, thus reducing the number of potential binding sites. Production of mAbs specific for FLC has been described previously but other groups have either found that their mAbs did not detect FLC from all neoplastic plasma cell clones tested, or, have not tested sufficient clones to be confident that the mAbs would detect the FLC from 100% of neoplastic clones. Hence, the purpose of this study was to prospectively assess the clinical utility of new highly-specific mouse anti-human FLC mAbs on a large number of consecutive patient samples. Anti-κ and anti-λ FLC mAbs were covalently coupled to different polystyrene Xmap® beads and assayed, simultaneously, in a multi-plex format by Luminex® (mAb assay). The mAbs displayed no cross-reactivity to bound LC, the alternate LC type, or other human proteins and had improved sensitivity (
Original languageEnglish
Pages (from-to)16
Number of pages1
JournalClinical Chemistry
Volume60
Issue number10
Publication statusPublished - 1 Jan 2014

Keywords

  • monoclonal antibody
  • immunoglobulin
  • epitope
  • antibody
  • paraprotein
  • polystyrene
  • protein
  • Bence Jones protein
  • antigen
  • light chain
  • urinalysis
  • patient
  • human
  • American
  • clinical chemistry
  • assay
  • clone
  • plasma cell
  • gold standard
  • cell clone
  • sheep
  • myeloma
  • multiple myeloma
  • mouse
  • plasma cell dyscrasia
  • monitoring
  • binding site
  • diagnosis
  • cross reaction
  • urine
  • polymerization
  • densitometry
  • electrophoresis
  • competitive inhibition
  • procedures
  • serum

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