Endothelial gene expression in kidney transplants with alloantibody indicates Antibody-mediated damage despite lack of C4d staining

Banu Sis, Gian S. Jhangri, Sakarn Bunnag, Kara Allanach, Bruce Kaplan, Philip F. Halloran

Research output: Contribution to journalArticle

328 Citations (Scopus)

Abstract

Anti-HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody-mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial-associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T-cell-mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody-mediated allograft damage and poor graft outcome.

Original languageEnglish (US)
Pages (from-to)2312-2323
Number of pages12
JournalAmerican Journal of Transplantation
Volume9
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Isoantibodies
Staining and Labeling
Transplants
Kidney
Gene Expression
Antibodies
Graft Rejection
Allografts
Biopsy
Microcirculation

Keywords

  • Antibody mediated rejection
  • C4d
  • Endothelial cells
  • Gene expression
  • Microarrays
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Endothelial gene expression in kidney transplants with alloantibody indicates Antibody-mediated damage despite lack of C4d staining. / Sis, Banu; Jhangri, Gian S.; Bunnag, Sakarn; Allanach, Kara; Kaplan, Bruce; Halloran, Philip F.

In: American Journal of Transplantation, Vol. 9, No. 10, 10.2009, p. 2312-2323.

Research output: Contribution to journalArticle

Sis, Banu ; Jhangri, Gian S. ; Bunnag, Sakarn ; Allanach, Kara ; Kaplan, Bruce ; Halloran, Philip F. / Endothelial gene expression in kidney transplants with alloantibody indicates Antibody-mediated damage despite lack of C4d staining. In: American Journal of Transplantation. 2009 ; Vol. 9, No. 10. pp. 2312-2323.
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