Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology

Enver Akalin, Rose C. Hendrix, Rathna Giri Polavarapu, Thomas C. Pearson, John F. Neylan, Christian P. Larsen, Fadi G. Lakkis

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Background. High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously. Methods. Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip®, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples. Results. Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>four-fold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-γ, T-cell receptor active β-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently upregulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyl-transferase, macrophage inflammatory protein-3β,-myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected. Conclusions. High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.

Original languageEnglish (US)
Pages (from-to)948-953
Number of pages6
JournalTransplantation
Volume72
Issue number5
StatePublished - Sep 15 2001
Externally publishedYes

Fingerprint

Allografts
Technology
Kidney
Biopsy
Gene Expression
Genes
Interferons
Up-Regulation
Monokines
Macrophage Inflammatory Proteins
Complement C3
Phosphoproteins
Antigen Presentation
Transferases
T-Cell Antigen Receptor
Interleukin-2
Intercellular Signaling Peptides and Proteins
Proteins
T-Lymphocytes

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Akalin, E., Hendrix, R. C., Giri Polavarapu, R., Pearson, T. C., Neylan, J. F., Larsen, C. P., & Lakkis, F. G. (2001). Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. Transplantation, 72(5), 948-953.

Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. / Akalin, Enver; Hendrix, Rose C.; Giri Polavarapu, Rathna; Pearson, Thomas C.; Neylan, John F.; Larsen, Christian P.; Lakkis, Fadi G.

In: Transplantation, Vol. 72, No. 5, 15.09.2001, p. 948-953.

Research output: Contribution to journalArticle

Akalin, E, Hendrix, RC, Giri Polavarapu, R, Pearson, TC, Neylan, JF, Larsen, CP & Lakkis, FG 2001, 'Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology', Transplantation, vol. 72, no. 5, pp. 948-953.
Akalin E, Hendrix RC, Giri Polavarapu R, Pearson TC, Neylan JF, Larsen CP et al. Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. Transplantation. 2001 Sep 15;72(5):948-953.
Akalin, Enver ; Hendrix, Rose C. ; Giri Polavarapu, Rathna ; Pearson, Thomas C. ; Neylan, John F. ; Larsen, Christian P. ; Lakkis, Fadi G. / Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. In: Transplantation. 2001 ; Vol. 72, No. 5. pp. 948-953.
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abstract = "Background. High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously. Methods. Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip{\circledR}, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples. Results. Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>four-fold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-γ, T-cell receptor active β-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently upregulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyl-transferase, macrophage inflammatory protein-3β,-myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected. Conclusions. High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.",
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AU - Akalin, Enver

AU - Hendrix, Rose C.

AU - Giri Polavarapu, Rathna

AU - Pearson, Thomas C.

AU - Neylan, John F.

AU - Larsen, Christian P.

AU - Lakkis, Fadi G.

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N2 - Background. High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously. Methods. Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip®, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples. Results. Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>four-fold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-γ, T-cell receptor active β-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently upregulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyl-transferase, macrophage inflammatory protein-3β,-myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected. Conclusions. High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.

AB - Background. High-density oligoarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. Oligoarray analysis of genes expressed during human renal allograft rejection has not been reported previously. Methods. Seven human renal allograft biopsies with histologic evidence of acute cellular rejection and three renal allograft biopsies without evidence of rejection (control) were analyzed for the expression of 6800 human genes using high-density oligoarrays (GeneChip®, Affymetrix, Santa Clara, CA). Quantitative expression of gene transcripts was determined and a comparison analysis between acute rejection and control biopsy samples was performed. Up-regulation of a specific gene transcript during acute rejection was considered to be significant if transcript abundance increased fourfold or more relative to control biopsy samples. Results. Comparison analysis revealed that between 32 and 219 gene transcripts are up-regulated (>four-fold) during acute rejection. Of these transcripts, only four (human monokine induced by interferon-γ, T-cell receptor active β-chain protein, interleukin-2 stimulated phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were consistently upregulated in each acute rejection sample relative to at least two of three control biopsy samples. Six other genes were up-regulated in six of seven acute rejection samples. These were interferon-stimulated growth factor-3, complement factor 3, nicotinamide N-methyl-transferase, macrophage inflammatory protein-3β,-myeloid differentiation protein, and CD18. Only two gene transcripts were down-regulated in five of seven acute rejection samples. Significant up-regulation of cytotoxic T-cell effector molecules, previously reported as markers of acute renal rejection in humans, was not detected. Conclusions. High-density oligoarray technology is useful for screening gene expression in transplanted tissues undergoing acute rejection. Because this method does not rely on a priori knowledge of which genes are involved in acute rejection, it is likely to yield novel insights into the mechanisms and diagnosis of rejection.

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