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

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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

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Spivey, T. L., Uccellini, L., Ascierto, M. L., Zoppoli, G., De Giorgi, V., Delogu, L. G., Engle, A. M., Thomas, J. M., Wang, E., Marincola, F. M., & Bedognetti, D. (2011). Gene expression profiling in acute allograft rejection: Challenging the immunologic constant of rejection hypothesis. Journal of translational medicine, 9(1), [174]. https://doi.org/10.1186/1479-5876-9-174