Systemic AA Amyloidosis

Systemic AA amyloidosis is a rare complication of chronic inflammatory disorders. The amyloid fibrils are derived from serum amyloid A protein, an acute phase protein synthesized in the liver. Clinical presentation is most commonly due to the consequences

  • PDF / 1,262,654 Bytes
  • 24 Pages / 439 x 666 pts Page_size
  • 30 Downloads / 207 Views

DOWNLOAD

REPORT


Systemic AA Amyloidosis Jennifer H. Pinney and Helen J. Lachmann

Abstract Systemic AA amyloidosis is a rare complication of chronic inflammatory disorders. The amyloid fibrils are derived from serum amyloid A protein, an acute phase protein synthesized in the liver. Clinical presentation is most commonly due to the consequences of renal involvement, with proteinuria and progressive renal decline. Progression to end stage renal failure is common. Management is currently centred on reducing the supply of the precursor protein by treating the underlying inflammatory condition, whilst supporting the affected organs. Monitoring of the serum amyloid A protein is vital to assess whether there is adequate suppression of the underlying disease. The level of serum amyloid A protein is a powerful predictor of both patient survival and renal outcome. In patients with adequate suppression of the serum amyloid A protein amyloid deposits can be seen to regress and renal function can be stabilised and even improve. Keywords Inflammation · Proteinuria · Nephrotic syndrome · Immunosuppression · SAP scintigraphy · End stage renal failure · Dialysis · Transplantation

20.1

Introduction

Systemic AA amyloidosis can complicate any chronic inflammatory disorder. The amyloid fibrils are derived from the acute phase protein, serum amyloid A protein (SAA), an apolipoprotein constituent of high density lipoprotein, (Parmelee et al. 1982) which is synthesized by hepatocytes under the transcriptional regulation of proinflammatory cytokines (Yamada 1999). AA amyloidosis is the third commonest type J. H. Pinney () National Amyloidosis Centre and Centre for Nephrology, Division of Medicine, UCL Medical School, Rowland Hill Street, London NW3 2PF, UK e-mail: [email protected] National Amyloidosis Centre and Centre for Nephrology, Division of Medicine, UCL Medical School, Royal Free Campus, London NW3 2QG, UK H. J. Lachmann National Amyloidosis Centre and Centre for Nephrology, Division of Medicine, UCL Medical School, Royal Free Campus, London NW3 2QG, UK e-mail: [email protected]

J. R. Harris (ed.), Protein Aggregation and Fibrillogenesis in Cerebral 541 and Systemic Amyloid Disease, Subcellular Biochemistry 65, DOI 10.1007/978-94-007-5416-4_20, © Springer Science+Business Media Dordrecht 2012

542

J. H. Pinney and H. J. Lachmann

of systemic amyloidosis diagnosed in the UK and is responsible for approximately 10 % of new cases seen each year. Presentation is usually with proteinuria and impaired renal function. Diagnosis is most commonly made on a renal biopsy. Targeted management is through suppression of the underlying inflammatory condition and serial quantification of SAA levels are an invaluable part of disease monitoring.

20.2 20.2.1

Pathogenesis of AA Amyloidosis Fibril Formation

Amyloid fibrils in AA amyloidosis are derived from the acute phase reactant, serum amyloid A protein (SAA) (Parmelee et al. 1982). SAA is an apolipoprotein, which, like C-reactive protein (CRP) is synthesized by hepatocytes under the transcriptional