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Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology
E Akalin1, R C Hendrix, R G Polavarapu
1Renal Division, Department of Medicine, Transplantation Section, Emory University, Atlanta, Georgia, USA.
Transplantation
|September 26, 2001
Summary
High-density oligoarray technology identified novel gene expression patterns in human renal allograft rejection. This method offers new insights into rejection mechanisms and diagnosis without prior gene knowledge.
Area of Science:
- Nephrology
- Immunology
- Genomics
Background:
- Human renal allograft rejection is a significant clinical challenge.
- Gene expression profiling offers a novel approach to understanding rejection.
- Previous studies have not utilized high-density oligoarrays for this purpose.
Purpose of the Study:
- To investigate gene expression profiles in human renal allograft rejection using high-density oligoarray technology.
- To identify genes consistently up-regulated or down-regulated during acute cellular rejection.
Main Methods:
- Analysis of 6800 human genes using high-density oligoarrays (GeneChip, Affymetrix).
- Comparison of gene expression between seven acute rejection and three control renal allograft biopsies.
- Definition of significant up-regulation as a fourfold or greater increase in transcript abundance.
Main Results:
- Between 32 and 219 gene transcripts were up-regulated (>fourfold) during acute rejection.
- Four genes (human monokine induced by interferon-gamma, T-cell receptor active beta-chain protein, interleukin-2 stimulated phosphoprotein, and RING4) were consistently up-regulated.
- Unexpectedly, significant up-regulation of known cytotoxic T-cell effector molecules was not detected.
Conclusions:
- High-density oligoarray technology is effective for screening gene expression in transplanted tissues during rejection.
- This unbiased approach can reveal novel insights into the mechanisms and diagnosis of renal allograft rejection.