Cytotoxicity of amyloidogenic immunoglobulin light chains in cell culture

L. A. Sikkink, M. Ramirez-Alvarado

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Light-chain amyloidosis (AL) is a devastating protein-misfolding disease characterized by abnormal proliferation of plasma cells in the bone marrow that secrete monoclonal immunoglobulin light chains that misfold and form amyloid fibrils, thus causing organ failure and death. Numerous reports on different protein-misfolding diseases show that soluble oligomeric species populated by amyloidogenic proteins can be quite toxic to cells. However, it is not well established whether the soluble immunoglobulin light-chain species found in circulation in patients with AL are toxic to cells in target organs. We determined the cellular toxicity of two well-characterized light-chain variable domain proteins from cardiac AL patients and their corresponding germline protein, devoid of somatic mutations. Our results show that the soluble form of the AL proteins we characterized are toxic to cardiomyocytes, and that the species found in cell culture correspond, for the most part, to the species present in circulation in these patients.

Original languageEnglish (US)
Article numbere98
JournalCell Death and Disease
Issue number11
StatePublished - Nov 2010


  • Apoptosis
  • Cellular toxicity
  • Immunoglobulin light chain
  • Light-chain amyloidosis
  • Protein misfolding

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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