title: Increased intragraft rejection-associated gene transcripts in patients with donor-specific antibodies and normal biopsies.
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.
authors.affiliation: Division of Pediatric Nephrology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hayde
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, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bao
authors.affiliation: 1] Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA [2] Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Graciela
authors.initials: G
authors.lastname: de Boccardo
authors.affiliation: 1] Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA [2] Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lubetzky
authors.affiliation: 1] Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA [2] Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ajaimy
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, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Colovai
authors.affiliation: Division of Computational Genetics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Golden
authors.affiliation: 1] Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, New York, USA [2] Division of Nephrology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Enver
authors.initials: E
authors.lastname: Akalin
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000328:Adult; D000906:Antibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014158:Transcription, Genetic; D014181:Transplantation Immunology
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D012313:RNA