Molecular correlates of scarring in kidney transplants

The emergence of mast cell transcripts

M. Mengel, J. Reeve, S. Bunnag, G. Einecke, B. Sis, T. Mueller, B. Kaplan, P. F. Halloran

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalAmerican Journal of Transplantation
Volume9
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Mast Cells
Cicatrix
Transplants
Kidney
Allografts
Biopsy
Graft Survival
B-Lymphocytes
Microarray Analysis
Plasma Cells
Interferon-gamma
Immunoglobulins
Macrophages
Inflammation
T-Lymphocytes
Wounds and Injuries

Keywords

  • Banff schema
  • Inflammation
  • Interstitial fibrosis
  • Microarrays
  • Pathology of renal transplantation
  • Tubular atrophy

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Molecular correlates of scarring in kidney transplants : The emergence of mast cell transcripts. / Mengel, M.; Reeve, J.; Bunnag, S.; Einecke, G.; Sis, B.; Mueller, T.; Kaplan, B.; Halloran, P. F.

In: American Journal of Transplantation, Vol. 9, No. 1, 01.2009, p. 169-178.

Research output: Contribution to journalArticle

Mengel, M, Reeve, J, Bunnag, S, Einecke, G, Sis, B, Mueller, T, Kaplan, B & Halloran, PF 2009, 'Molecular correlates of scarring in kidney transplants: The emergence of mast cell transcripts', American Journal of Transplantation, vol. 9, no. 1, pp. 169-178. https://doi.org/10.1111/j.1600-6143.2008.02462.x
Mengel, M. ; Reeve, J. ; Bunnag, S. ; Einecke, G. ; Sis, B. ; Mueller, T. ; Kaplan, B. ; Halloran, P. F. / Molecular correlates of scarring in kidney transplants : The emergence of mast cell transcripts. In: American Journal of Transplantation. 2009 ; Vol. 9, No. 1. pp. 169-178.
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