Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies

Anjali Gupta, Pilib Ó Broin, Y. Bao, James M. Pullman, Layla Kamal, Maria Ajaimy, Michelle Lubetzky, Adriana Colovai, Daniel Schwartz, Graciela de Boccardo, Aaron Golden, Enver Akalin

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Abstract

The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1–3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell–associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA–selective transcripts was found in the biopsies of C4d− Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA–selective gene transcripts may be used as molecular markers for AMR, especially in C4d− biopsies.Kidney International advance online publication, 30 September 2015; doi:10.1038/ki.2015.276.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - Sep 30 2015

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Inflammation
Transplants
Kidney
Biopsy
Transcriptome
Antibodies
Tissue Donors
Regulatory T-Lymphocytes
Interferons
Publications
Anti-Idiotypic Antibodies
Incidence
Genes

ASJC Scopus subject areas

  • Nephrology

Cite this

Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies. / Gupta, Anjali; Ó Broin, Pilib; Bao, Y.; Pullman, James M.; Kamal, Layla; Ajaimy, Maria; Lubetzky, Michelle; Colovai, Adriana; Schwartz, Daniel; de Boccardo, Graciela; Golden, Aaron; Akalin, Enver.

In: Kidney International, 30.09.2015.

Research output: Contribution to journalArticle

Gupta, Anjali ; Ó Broin, Pilib ; Bao, Y. ; Pullman, James M. ; Kamal, Layla ; Ajaimy, Maria ; Lubetzky, Michelle ; Colovai, Adriana ; Schwartz, Daniel ; de Boccardo, Graciela ; Golden, Aaron ; Akalin, Enver. / Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies. In: Kidney International. 2015.
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