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Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass.
Cristoferi, Iacopo; Varol, Hilal; van Baardwijk, Myrthe; Rahiem, Layla; Lila, Karishma A; van den Bosch, Thierry P P; Baan, Carla C; Hesselink, Dennis A; Kramann, Rafael; Minnee, Robert C; Mustafa, Dana A M; Reinders, Marlies E J; Roelen, Dave L; Shahzad-Arshad, Shazia P; Smith, Rex N; Stubbs, Andrew P; Colvin, Robert B; Rosales, Ivy A; Clahsen-van Groningen, Marian C.
Afiliação
  • Cristoferi I; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands; Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Rotterdam, the Netherlands. Electronic address: i.cristoferi@erasmusmc.nl.
  • Varol H; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • van Baardwijk M; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands; Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Rahiem L; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Lila KA; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • van den Bosch TPP; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Baan CC; Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Hesselink DA; Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Kramann R; Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Rotterdam, the Netherlands; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany; Department of Nephrology and Clinical Immunology, University Hosp
  • Minnee RC; Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Mustafa DAM; Department of Pathology and Clinical Bioinformatics, the Tumor Immuno-Pathology Laboratory, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Reinders MEJ; Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Roelen DL; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
  • Shahzad-Arshad SP; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Smith RN; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Stubbs AP; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands.
  • Colvin RB; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Rosales IA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Clahsen-van Groningen MC; Department of Pathology and Clinical Bioinformatics, Erasmus MC Transplant Institute, Rotterdam, the Netherlands; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany. Electronic address: m.clahsen-vangroningen@erasmusmc.nl.
Kidney Int ; 105(4): 812-823, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38128610
ABSTRACT
Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) > 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody-mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher glomerular abundance of natural killer cells and higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, interstitial fibrosis tubular atrophy, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher glomerular abundance and activity of T cells (CD3+, CD3+CD8+, and CD3+CD8-). Thus, we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell dominant phenotype.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Nefropatias Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Nefropatias Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article