Antibody-mediated rejection with and without donor-specific anti-human leucocyte antigen antibodies: performance of the peripheral blood 8-gene expression assay.


Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
01 08 2020
Historique:
received: 24 02 2020
accepted: 03 04 2020
pubmed: 1 7 2020
medline: 16 12 2020
entrez: 29 6 2020
Statut: ppublish

Résumé

Recently a peripheral blood 8-gene expression assay was developed for non-invasive detection of antibody-mediated rejection (ABMR) after kidney transplantation. Its value has not yet been evaluated in detail in clinical scenarios with different baseline disease probability [human leucocyte antigen donor-specific antibodies (HLA-DSA)-positive versus HLA-DSA-negative cases at the time of stable graft function versus graft dysfunction]. Here we investigated the diagnostic accuracy of the 8-gene expression assay for histology of ABMR (ABMRh) with or without HLA-DSA in a cross-sectional cohort study of 387 blood samples with a concomitant graft biopsy. In patients with HLA-DSA (n = 64), the 8-gene expression assay discriminated DSA-positive ABMRh (DSAposABMRh) cases (n = 16) with good diagnostic performance {area under the receiver operating characteristic curve [AUROC] 83.1% [95% confidence interval (CI) 70.8-95.3]}. Also, in HLA-DSA-negative samples (n = 323), a clinically relevant diagnostic performance for DSAnegABMRh cases was found (n = 30) with an AUROC of 75.8% (95% CI 67.4-84.4). The 8-gene assay did not discriminate DSAposABMRh cases from DSAnegABMRh cases. There was a net benefit for clinical decision-making when adding the 8-gene expression assay to a clinical model consisting of estimated glomerular filtration rate, proteinuria, HLA-DSA and age. The 8-gene expression assay shows great potential for implementation in the clinical follow-up of high-risk HLA-DSA-positive patients and clinical relevance in HLA-DSA-negative cases.

Sections du résumé

BACKGROUND
Recently a peripheral blood 8-gene expression assay was developed for non-invasive detection of antibody-mediated rejection (ABMR) after kidney transplantation. Its value has not yet been evaluated in detail in clinical scenarios with different baseline disease probability [human leucocyte antigen donor-specific antibodies (HLA-DSA)-positive versus HLA-DSA-negative cases at the time of stable graft function versus graft dysfunction].
METHODS
Here we investigated the diagnostic accuracy of the 8-gene expression assay for histology of ABMR (ABMRh) with or without HLA-DSA in a cross-sectional cohort study of 387 blood samples with a concomitant graft biopsy.
RESULTS
In patients with HLA-DSA (n = 64), the 8-gene expression assay discriminated DSA-positive ABMRh (DSAposABMRh) cases (n = 16) with good diagnostic performance {area under the receiver operating characteristic curve [AUROC] 83.1% [95% confidence interval (CI) 70.8-95.3]}. Also, in HLA-DSA-negative samples (n = 323), a clinically relevant diagnostic performance for DSAnegABMRh cases was found (n = 30) with an AUROC of 75.8% (95% CI 67.4-84.4). The 8-gene assay did not discriminate DSAposABMRh cases from DSAnegABMRh cases. There was a net benefit for clinical decision-making when adding the 8-gene expression assay to a clinical model consisting of estimated glomerular filtration rate, proteinuria, HLA-DSA and age.
CONCLUSION
The 8-gene expression assay shows great potential for implementation in the clinical follow-up of high-risk HLA-DSA-positive patients and clinical relevance in HLA-DSA-negative cases.

Identifiants

pubmed: 32594133
pii: 5864472
doi: 10.1093/ndt/gfaa096
doi:

Substances chimiques

Biomarkers 0
HLA Antigens 0
Isoantibodies 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1328-1337

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Auteurs

Elisabet Van Loon (E)

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.

Evelyne Lerut (E)

Department of Morphology and Molecular Pathology, University Hospitals Leuven, Leuven, Belgium.

Henriette de Loor (H)

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.

Dirk Kuypers (D)

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.

Marie-Paule Emonds (MP)

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.
Histocompatibility and Immunogenetic Laboratory, Red Cross-Flanders, Mechelen, Belgium.

Dany Anglicheau (D)

Paris Descartes, Sorbonne Paris Cité University, INSERM U1151, Paris, France.
Department of Nephrology and Kidney Transplantation, RTRS Centaure, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Wilfried Gwinner (W)

Department of Nephrology, Hannover Medical School, Hannover, Germany.

Marie Essig (M)

CHU Limoges, Department of Nephrology, Dialysis and Transplantation, University of Limoges, U850 INSERM, Limoges, France.

Pierre Marquet (P)

CHU Limoges, University of Limoges, U850 INSERM, Limoges, France.

Maarten Naesens (M)

KU Leuven Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Leuven, Belgium.
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.

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Classifications MeSH