Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings

Elisabet Van Loon, Baptiste Lamarthée, Thomas Barba, Sandra Claes, Maarten Coemans, Henriette de Loor, Marie Paule Emonds, Priyanka Koshy, Dirk Kuypers, Paul Proost, Aleksandar Senev, Ben Sprangers, Claire Tinel, Olivier Thaunat, Amaryllis H. Van Craenenbroeck, Dominique Schols, Maarten Naesens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation.

Original languageEnglish (US)
Article number818569
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Feb 23 2022

Funding

We thank the clinicians and surgeons, nursing staff, and the patients of University Hospitals Leuven. EVL holds a fellowship grant (1143919N) from The Research Foundation Flanders (F.W.O.). MN is a senior clinical investigator of F.W.O. (1844019N) and is supported by an F.W.O TBM grant (grant no. T004417N), an F.W.O. junior project grant (grant no. G087620N), an ERACoSysMed H2020 grant (grant no. JTC2_29), and a C3 internal grant from the KU Leuven (grant no. C32/17/049).

Keywords

  • allograft rejection
  • chemokines
  • cytokines
  • donor-specific anti-HLA antibodies
  • kidney transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings'. Together they form a unique fingerprint.

Cite this