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Rheumatology Advance Access originally published online on September 24, 2008
Rheumatology 2008 47(11):1651-1654; doi:10.1093/rheumatology/ken371
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1: potential explanation for higher risk of type AA amyloidosis

J. C. H. van der Hilst1, T. Yamada2, H. J. M. Op den Camp3, J. W. M. van der Meer1, J. P. H. Drenth4 and A. Simon1

1Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 2Department of Clinical Laboratory Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan 3Department of Microbiology, IWWR, Radboud University and 4Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Correspondence to: J. C. H. van der Hilst, Department of General Internal Medicine (463), Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands. E-mail: j.vanderhilst{at}aig.umcn.nl


  Abstract

Objective. Genetic polymorphisms in serum amyloid A (SAA) have been shown to substantially influence the risk of developing type AA amyloidosis. Recently, a role for MMP-1 has been suggested in the pathogenesis of AA amyloidosis. Therefore, we investigated if the SAA1 isotypes are differentially degraded by MMP-1.

Methods. Degradation of different SAA isotypes by MMP-1 was assessed by immunoblotting. MALDI-TOF mass spectrometry was used to identify degradation fragments.

Results. We found that SAA1.5 is more resistant to degradation by MMP-1 than SAA1.1. This difference is caused by the capacity of MMP-1 to cleave at the site of the polymorphism at position 57.

Conclusion. These results may explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons with a SAA1.5 genotype.

KEY WORDS: AA amyloidosis, Matrix metalloproteinase

Submitted 29 April 2008; revised version accepted 12 August 2008.
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