Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study

Rivka Goldis, Batia Kaplan*, Michael Arad, Angela Dispenzieri, Surendra Dasari, Olga Lesya Kukuy, Amos J. Simon, Amir Dori, Efrat Shavit-Stein, Tamar Ziv, David Murray, Taxiarchis Kourelis, Morie A. Gertz, Dan Dominissini, Hila Magen, Eli Muchtar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Diagnosis of light chain amyloidosis (AL) requires demonstration of amyloid deposits in a tissue biopsy followed by appropriate typing. Previous studies demonstrated increased dimerization of monoclonal serum free light chains (FLCs) as a pathological feature of AL. To further examine the pathogenicity of FLC, we aimed at testing amino acid sequence homology between circulating and deposited light chains (LCs). Methods: Matched tissue biopsy and serum of 10 AL patients were subjected to tissue proteomic amyloid typing and nephelometric FLC assay, respectively. Serum FLC monomers (M) and dimers (D) were analyzed by Western blotting (WB) and mass spectrometry (MS). Results: WB of serum FLCs showed predominance of either κ or λ type, in agreement with the nephelometric assay data. Abnormal FLC M-D patterns typical of AL amyloidosis were demonstrated in 8 AL-λ patients and in one of two AL-κ patients: increased levels of monoclonal FLC dimers, high D/M ratio values of involved FLCs, and high ratios of involved to uninvolved dimeric FLCs. MS of serum FLC dimers showed predominant constant domain sequences, in concordance with the tissue proteomic amyloid typing. Most importantly, variable domain sequence homology between circulating and deposited LC species was demonstrated, mainly in AL-λ cases. Conclusions: This is the first study to demonstrate homology between circulating FLCs and tissue-deposited LCs in AL-λ amyloidosis. The applied methodology can facilitate studying the pathogenicity of circulating FLC dimers in AL amyloidosis. The study also highlights the potential of FLC monomer and dimer analysis as a non-invasive screening tool for this disease.

Original languageEnglish
Pages (from-to)464-471
Number of pages8
JournalClinical Chemistry and Laboratory Medicine
Volume62
Issue number3
DOIs
StatePublished - 1 Feb 2024

Keywords

  • amyloidosis
  • dimers
  • free light chains
  • mass spectrometry
  • monomers
  • western blotting

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