Gene expression profiling in acute allograft rejection: Challenging the immunologic constant of rejection hypothesis

Tara L. Spivey, Lorenzo Uccellini, Maria L. Ascierto, Gabriele Zoppoli, Valeria De Giorgi, Lucia G. Delogu, Alyson M. Engle, Jaime M. Thomas, Ena Wang, Francesco M. Marincola, Davide Bedognetti

Research output: Contribution to journalReview article

58 Citations (Scopus)

Abstract

In humans, the role and relationship between molecular pathways that lead to tissue destruction during acute allograft rejection are not fully understood. Based on studies conducted in humans, we recently hypothesized that different immune-mediated tissue destruction processes (i.e. cancer, infection, autoimmunity) share common convergent final mechanisms. We called this phenomenon the "Immunologic Constant of Rejection (ICR)." The elements of the ICR include molecular pathways that are consistently described through different immune-mediated tissue destruction processes and demonstrate the activation of interferon-stimulated genes (ISGs), the recruitment of cytotoxic immune cells (primarily through CXCR3/CCR5 ligand pathways), and the activation of immune effector function genes (IEF genes; granzymes A/B, perforin, etc.).Here, we challenge the ICR hypothesis by using a meta-analytical approach and systematically reviewing microarray studies evaluating gene expression on tissue biopsies during acute allograft rejection. We found the pillars of the ICR consistently present among the studies reviewed, despite implicit heterogeneity.Additionally, we provide a descriptive mechanistic overview of acute allograft rejection by describing those molecular pathways most frequently encountered and thereby thought to be most significant. The biological role of the following molecular pathways is described: IFN-γ, CXCR3/CCR5 ligand, IEF genes, TNF-α, IL-10, IRF-1/STAT-1, and complement pathways. The role of NK cell, B cell and T-regulatory cell signatures are also addressed.

Original languageEnglish
Article number174
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
Publication statusPublished - 12 Oct 2011
Externally publishedYes

Fingerprint

Gene Expression Profiling
Gene expression
Allografts
Genes
Tissue
Granzymes
Chemical activation
Complement C1
Ligands
Perforin
Biopsy
Regulatory T-Lymphocytes
Microarrays
Autoimmunity
Natural Killer Cells
Interleukin-10
Interferons
B-Lymphocytes
Cells
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gene expression profiling in acute allograft rejection : Challenging the immunologic constant of rejection hypothesis. / Spivey, Tara L.; Uccellini, Lorenzo; Ascierto, Maria L.; Zoppoli, Gabriele; De Giorgi, Valeria; Delogu, Lucia G.; Engle, Alyson M.; Thomas, Jaime M.; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide.

In: Journal of Translational Medicine, Vol. 9, No. 1, 174, 12.10.2011.

Research output: Contribution to journalReview article

Spivey, TL, Uccellini, L, Ascierto, ML, Zoppoli, G, De Giorgi, V, Delogu, LG, Engle, AM, Thomas, JM, Wang, E, Marincola, FM & Bedognetti, D 2011, 'Gene expression profiling in acute allograft rejection: Challenging the immunologic constant of rejection hypothesis', Journal of Translational Medicine, vol. 9, no. 1, 174. https://doi.org/10.1186/1479-5876-9-174
Spivey, Tara L. ; Uccellini, Lorenzo ; Ascierto, Maria L. ; Zoppoli, Gabriele ; De Giorgi, Valeria ; Delogu, Lucia G. ; Engle, Alyson M. ; Thomas, Jaime M. ; Wang, Ena ; Marincola, Francesco M. ; Bedognetti, Davide. / Gene expression profiling in acute allograft rejection : Challenging the immunologic constant of rejection hypothesis. In: Journal of Translational Medicine. 2011 ; Vol. 9, No. 1.
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