Clinical aspects of systemic amyloid diseases

Laura Obici, Vittorio Perfetti, Giovanni Palladini, Remigio Moratti, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review

Abstract

Amyloidosis is a protein misfolding disorder in which soluble proteins aggregate as insoluble amyloid fibrils. Protein aggregates and amyloid fibrils cause functional and structural organ damage respectively. To date, at least 24 different proteins have been recognized as causative agents of amyloid diseases, localized or systemic. The two most common forms of systemic amyloidosis are light-chain (AL) amyloidosis and reactive AA amyloidosis due to chronic inflammatory diseases. β2-microglobulin amyloidosis is a common complication associated with long-term hemodialysis. Hereditary systemic amyloidoses are a group of autosomal dominant disorders caused by mutations in the genes of several plasma proteins. Heterogeneity in clinical presentation, pattern of amyloid-related organ toxicity and rate of disease progression is observed among systemic amyloidoses. In particular, β2- microglobulin presents unique clinical features compared to the other systemic forms. The phenotypic features of hereditary systemic amyloidoses may instead overlap those of the two more common forms of acquired amyloidoses mentioned above and therefore a correct diagnosis can not rely only on clinical grounds. Unequivocal identification of the deposited protein is essential in order to avoid misdiagnosis and inappropriate treatment. Amyloid deposits can be reabsorbed and organ dysfunction reversed if the concentration of the amyloidogenic protein is reduced or zeroed. At present, the most effective approach to treatment of the systemic amyloidoses involves shutting down, or substantially reducing the synthesis of the amyloid precursor, or, as in the case of β2-microglobulin, promoting its clearance.

Original languageEnglish
Pages (from-to)11-22
Number of pages12
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1753
Issue number1
DOIs
Publication statusPublished - Nov 10 2005

Keywords

  • β- microglobulin
  • Chemotherapy
  • Chronic inflammation
  • Hereditary amyloidosis
  • Immunoglobulin light-chain
  • Transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics

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