Thermal stability threshold for amyloid formation in light chain amyloidosis

Tanya L. Poshusta, Nagaaki Katoh, Morie Gertz, Angela Dispenzieri, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.

Original languageEnglish (US)
Pages (from-to)22604-22617
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume14
Issue number11
DOIs
StatePublished - Nov 15 2013

Fingerprint

Amyloidosis
Amyloid
Thermodynamic stability
thermal stability
Hot Temperature
Light
thresholds
organs
Immunoglobulin Light Chains
proteins
Proteins
stem cells
Amyloid Plaques
kinetics
kidneys
Therapeutics
chemotherapy
Transplants
Kinetics
Chemotherapy

Keywords

  • Amyloid fibril formation
  • Hematologic response
  • Immunoglobulin light chain
  • Light chain amyloidosis
  • Organ response
  • Partially folded states
  • Thermodynamic stability

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Thermal stability threshold for amyloid formation in light chain amyloidosis. / Poshusta, Tanya L.; Katoh, Nagaaki; Gertz, Morie; Dispenzieri, Angela; Ramirez-Alvarado, Marina.

In: International Journal of Molecular Sciences, Vol. 14, No. 11, 15.11.2013, p. 22604-22617.

Research output: Contribution to journalArticle

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