Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease

To identify systemic cytokine patterns in Chronic Graft-versus-Host-Disease (CGVHD), we profiled the gene expression of circulating monocytes. Pathway analysis identified two gene sets that were significantly upregulated across a broad range of patients with inflammatory and sclerotic presentations: (1) genes induced by Type I and Type II IFN, and (2) receptor genes for innate immune responses to cellular damage. Multiple IFN-inducible genes involved in signal transduction, anti-viral function, lymphocyte homeostasis, trafficking, and antigen presentation were increased. Furthermore, upregulation of TLR/NLR/CLR receptor genes for nucleic acids, ribonucleoproteins and annexin implicated response to damaged cells as a source of activation of inflammasomes and induction of Type I IFN.

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Hakim FT, Memon S, Jin P, Imanguli MM, Wang H, Rehman N, Yan XY, Rose J, Mays JW, Dhamala S, Kapoor V, Telford W, Dickinson J, Davis S, Halverson D, Naik HB, Baird K, Fowler D, Stroncek D, Cowen EW, Pavletic SZ, Gress RE