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

Frontiers in Immunology

Priyanka Koshy¹  Sandra Claes²  Dominique Schols²  Henriette de Loor³  Claire Tinel³  Baptiste Lamarthée³  Maarten Naesens⁴  Amaryllis H. Van Craenenbroeck⁴  Dirk Kuypers⁴  Elisabet Van Loon⁴  Thomas Barba⁵  Olivier Thaunat⁵  Aleksandar Senev⁶  Marie-Paule Emonds⁶  Ben Sprangers⁷  Paul Proost⁷  Maarten Coemans⁸ 

[1] Department of Imaging and Pathology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium;Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Katholieke Universiteit (KU) Leuven, Leuven, Belgium;Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, Katholieke Universiteit (KU) Leuven, Leuven, Belgium;Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium;Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital Lyon, Hospices Civils de Lyon, Lyon, France;Histocompatibility and Immunogenetics Laboratory, Red Cross-Flanders, Mechelen, Belgium;Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit (KU) Leuven, Leuven, Belgium;Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care, Katholieke Universiteit (KU) Leuven, Leuven, Belgium;

关键词: cytokines;    chemokines;    donor-specific anti-HLA antibodies;    allograft rejection;    kidney transplantation;   

DOI  :  10.3389/fimmu.2022.818569

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown