Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts
Version of Record online: 31 OCT 2008
© 2009 The Authors Journal compilation © 2009 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 9, Issue 1, pages 169–178, January 2009
How to Cite
Mengel, M., Reeve, J., Bunnag, S., Einecke, G., Sis, B., Mueller, T., Kaplan, B. and Halloran, P. F. (2009), Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts. American Journal of Transplantation, 9: 169–178. doi: 10.1111/j.1600-6143.2008.02462.x
- Issue online: 19 DEC 2008
- Version of Record online: 31 OCT 2008
- Received 07 July 2008, revised 14 August 2008 and accepted for publication 02 September 2008
- Banff schema;
- interstitial fibrosis;
- pathology of renal transplantation;
- tubular atrophy
In the Banff consensus, infiltrates in areas of scarring are ignored. This study aimed to characterize the molecular correlates and clinical significance of scarring and inflammation in scarred areas.
We assessed the extent of interstitial infiltrates, tubulitis and scarring in 129 clinically indicated renal allograft biopsies, and correlated the results with microarray expression data and allograft survival. Findings were validated in 50 additional biopsies.
Transplants with scarring had a worse prognosis if the scarred area showed infiltrates. Infiltration in unscarred and scarred areas was associated with reduced death censored graft survival. In microarray analysis, infiltration in unscarred areas strongly (>r ± 0.4) correlated with 484 transcripts associated with cytotoxic T cells, interferon-gamma, macrophages and injury. Scarring correlated with a distinct set of 172 transcripts associated with B cells, plasma cells, and others of unknown significance. The strongest correlation was with four mast cell transcripts. In biopsies with scarring, high expression of mast cell transcripts was associated with reduced graft survival and poor functional recovery.
In renal allograft biopsies, infiltrates in scarred areas have implications for poor outcomes. Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes.