Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies

Nicole A.M. Hayde, Pilib Ó Broin, Yi Bao, Graciela De Boccardo, Michelle Lubetzky, Maria Ajaimy, James M. Pullman, Adriana Colovai, Aaron Golden, Enver Akalin

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We investigated why some donor-specific antibody-positive patients do not develop antibody-mediated rejection. Of 71 donor-specific antibody-positive patients, 46 had diagnosis of antibody-mediated rejection and 25 had normal biopsies. Fifty donor-specific antibody-negative patients with normal biopsies were used as a control group. A subgroup of 61 patients with available biopsy and 64 with blood samples were analyzed by microarrays. Both donor-specific antibody-positive/antibody-mediated rejection-positive and negative biopsies showed increased expression of gene transcripts associated with cytotoxic T cells, natural killer cells, macrophages, interferon-gamma, and rejection compared to donor-specific antibody-negative biopsies. Regulatory T-cell transcripts were upregulated in donor-specific antibody-positive/antibody- mediated rejection-positive and B-cell transcripts in donor-specific antibody-positive/antibody-mediated rejection-negative biopsies. Whole-blood gene expression analysis showed increased immune activity in only donor-specific antibody-positive/antibody-mediated rejection-positive but not negative patients. During a median follow-up of 36 months, 4 donor-specific antibody-positive/antibody-mediated rejection-negative patients developed antibody-mediated rejection, 12 continued to have donor-specific antibody, but 9 lost their donor-specific antibody. Gene expression profiles did not predict the development of antibody-mediated rejection or the persistence of donor-specific antibody. Thus, donor-specific antibody-positive/antibody- mediated rejection-negative patients had increased rejection-associated gene transcripts in their allografts despite no histologic findings of rejection but not in their blood. This was found in both biopsy and blood samples of donor-specific antibody-positive/antibody-mediated rejection-positive patients.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalKidney International
Volume86
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Tissue Donors
Biopsy
Antibodies
Genes
Gene Expression
Regulatory T-Lymphocytes
Blood Donors
Transcriptome
Natural Killer Cells
Interferon-gamma

Keywords

  • antibody-mediated rejection
  • donor-specific anti-HLA antibodies
  • gene expression
  • microarrays

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies. / Hayde, Nicole A.M.; Broin, Pilib Ó; Bao, Yi; De Boccardo, Graciela; Lubetzky, Michelle; Ajaimy, Maria; Pullman, James M.; Colovai, Adriana; Golden, Aaron; Akalin, Enver.

In: Kidney International, Vol. 86, No. 3, 2014, p. 600-609.

Research output: Contribution to journalArticle

Hayde, Nicole A.M. ; Broin, Pilib Ó ; Bao, Yi ; De Boccardo, Graciela ; Lubetzky, Michelle ; Ajaimy, Maria ; Pullman, James M. ; Colovai, Adriana ; Golden, Aaron ; Akalin, Enver. / Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies. In: Kidney International. 2014 ; Vol. 86, No. 3. pp. 600-609.
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AB - We investigated why some donor-specific antibody-positive patients do not develop antibody-mediated rejection. Of 71 donor-specific antibody-positive patients, 46 had diagnosis of antibody-mediated rejection and 25 had normal biopsies. Fifty donor-specific antibody-negative patients with normal biopsies were used as a control group. A subgroup of 61 patients with available biopsy and 64 with blood samples were analyzed by microarrays. Both donor-specific antibody-positive/antibody-mediated rejection-positive and negative biopsies showed increased expression of gene transcripts associated with cytotoxic T cells, natural killer cells, macrophages, interferon-gamma, and rejection compared to donor-specific antibody-negative biopsies. Regulatory T-cell transcripts were upregulated in donor-specific antibody-positive/antibody- mediated rejection-positive and B-cell transcripts in donor-specific antibody-positive/antibody-mediated rejection-negative biopsies. Whole-blood gene expression analysis showed increased immune activity in only donor-specific antibody-positive/antibody-mediated rejection-positive but not negative patients. During a median follow-up of 36 months, 4 donor-specific antibody-positive/antibody-mediated rejection-negative patients developed antibody-mediated rejection, 12 continued to have donor-specific antibody, but 9 lost their donor-specific antibody. Gene expression profiles did not predict the development of antibody-mediated rejection or the persistence of donor-specific antibody. Thus, donor-specific antibody-positive/antibody- mediated rejection-negative patients had increased rejection-associated gene transcripts in their allografts despite no histologic findings of rejection but not in their blood. This was found in both biopsy and blood samples of donor-specific antibody-positive/antibody-mediated rejection-positive patients.

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