title: Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.
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.
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of Computational Genetics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Pilib Ó
authors.initials: PÓ
authors.lastname: Broin
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Pullman
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Layla
authors.initials: L
authors.lastname: Kamal
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ajaimy
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lubetzky
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Colovai
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schwartz
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Graciela
authors.initials: G
authors.lastname: de Boccardo
authors.affiliation: Division of Computational Genetics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA; Department of Mathematical Sciences, Yeshiva University, New York, New York, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Golden
authors.affiliation: Montefiore-Einstein Center for Transplantation, Albert Einstein College of Medicine, Bronx, New York, USA; Renal Division, Albert Einstein College of Medicine, Bronx, New York, USA. Electronic address: eakalin@montefiore.org.
authors.forename: Enver
authors.initials: E
authors.lastname: Akalin
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059467:Transcriptome; D014657:Vasculitis / Q000473:pathology*
chemical_list: D000906:Antibodies; D015415:Biomarkers; D006680:HLA Antigens; D007371:Interferon-gamma
keywords: antibody-mediated rejection; gene expression; glomerulitis; peritubular capillaritis