title: Intragraft gene expression in positive crossmatch kidney allografts: ongoing inflammation mediates chronic antibody-mediated injury.
abstract: We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR were performed on RNA from protocol renal allograft biopsies in three groups: (1) +XM/TG+ biopsies before and after TG; (2) +XM/NoTG; and (3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2447 genes (18%) and 3200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3718 probe sets were differentially expressed but these were over-represented in only four pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to the +XM/NoTG and control groups. In conclusion, pretransplant donor-specific anti-HLA antibodies results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of +XM grafts are exposed to chronic injury.
authors.affiliation: Department of Surgery, Division of Transplantation Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. dean.patrick2@mayo.edu
authors.forename: P G
authors.initials: PG
authors.lastname: Dean
authors.forename: W D
authors.initials: WD
authors.lastname: Park
authors.forename: L D
authors.initials: LD
authors.lastname: Cornell
authors.forename: J M
authors.initials: JM
authors.lastname: Gloor
authors.forename: M D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000906:Antibodies / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D016030:Kidney Transplantation; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies