Intragraft gene expression in positive crossmatch kidney allografts: Ongoing inflammation mediates chronic antibody-mediated injury

P. G. Dean, W. D. Park, L. D. Cornell, J. M. Gloor, M. D. Stegall

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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. The authors study intragraft gene expression profiles of positive crossmatch kidney transplant recipients and identify a gene expression profile characterized by inflammation and cellular infiltration in the recipients who develop transplant glomerulopathy.

Original languageEnglish (US)
Pages (from-to)1551-1563
Number of pages13
JournalAmerican Journal of Transplantation
Volume12
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Accommodation
  • anti-HLA antibody
  • kidney transplant
  • transplant glomerulopathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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