Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell Transcripts

https://doi.org/10.1111/j.1600-6143.2008.02462.xGet rights and content
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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.

key words

Banff schema
inflammation
interstitial fibrosis brosis
microarrays
pathology of renal transplantation
tubular atrophy

Abbreviations

ABMR
antibody-mediated rejection
BATs
B-cell-associated transcripts
CATs
cytotoxic T-cell-associated transcripts
GRITs
interferon-γ-dependent rejection-induced transcripts
IFNG
interferon-γ
IFTA
interstitial fibrosis and tubular atrophy
i-IFTA
inflammation in areas with interstitial fibrosis and tubular atrophy
i-Banff
inflammation in areas without interstitial fibrosis and tubular atrophy
IGTs
immunoglobulin transcripts
IRITs
injury and repair induced transcripts
MACATs
mast cell-associated transcripts
MATs
macrophage-associated transcripts
KTs
kidney transcripts, decreased in rejection
PBT
pathogenesis-based transcript set
TCMR
T-cell-mediated rejection

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