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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 EMAIL logo , 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 and Eli Muchtar
Published/Copyright: September 26, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 3

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.

Keywords: free light chains; monomers; dimers; amyloidosis; western blotting; mass spectrometry
Corresponding author: Batia Kaplan, PhD, Institute of Hematology and Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer 5265601, Ramat Gan, Israel, Phone: +972 54 764338, E-mail:

  1. Research ethics: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board (21-010372).

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: The study is supported by Pfizer Global Medical Grants; program 65925007.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2023-06-06
Accepted: 2023-09-12
Published Online: 2023-09-26
Published in Print: 2024-02-26

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-0591
Keywords for this article
free light chains; monomers; dimers; amyloidosis; western blotting; mass spectrometry

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Unraveling the mystery of blood groups and COVID-19
  4. Reviews
  5. Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis
  6. Platelet distribution width (PDW) as a significant correlate of COVID-19 infection severity and mortality
  7. Mini Reviews
  8. ABO blood group-related mechanism of infection of SARS-CoV-2: an overview of systematic reviews
  9. Opinion Paper
  10. Personalized laboratory medicine in the digital health era: recent developments and future challenges
  11. Guidelines and Recommendations
  12. Algorithm of differential diagnosis of anemia involving laboratory medicine specialists to advance diagnostic excellence
  13. General Clinical Chemistry and Laboratory Medicine
  14. Rescaling creatinine makes GFR estimation equations generally applicable across populations – validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry
  15. Periodic verification of results’ comparability between several analyzers: experience in the application of the EP31-A-IR guideline
  16. Machine learning to optimize cerebrospinal fluid dilution for analysis of MRZH reaction
  17. Diagnostic performance of automated red cell parameters in predicting bone marrow iron stores
  18. Reliability of hemoglobin A2 value as measured by the Premier Resolution system for screening of β-thalassemia carriers
  19. Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study
  20. Development of high-performance point-of-care aqueous VEGF detection system and proof-of-concept validation in RVO patients
  21. Detection rate of IGF-1 variants and their implication to protein binding: study of over 240,000 patients
  22. Analysis of a second-tier test panel in dried blood spot samples using liquid chromatography-tandem mass spectrometry in Catalonia’s newborn screening programme
  23. Targeted quantitative lipidomic uncovers lipid biomarkers for predicting the presence of compensated cirrhosis and discriminating decompensated cirrhosis from compensated cirrhosis
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  25. Establishment of reference intervals for free light chains and immunoglobulins in Saudi population
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  31. Infectious Diseases
  32. Monocyte distribution width as an early predictor of short-term outcome in adult patients with sepsis
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