• Konrad Buscher, Rebecca Rixen, Paula Schütz, Birte Hüchtmann, Veerle Van Marck, Barbara Heitplatz, Ulrich Jehn, Daniela A Braun, Gert Gabriëls, Hermann Pavenstädt, and Stefan Reuter.
• Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, Münster, Germany. Electronic address: konrad.buscher@ukmuenster.de.
• Transl Res. 2023 Dec 1; 262: 354335-43.

AbstractKidney transplantation causes large perturbations of the immune system. While many studies focus on the allograft, insights into systemic effects are largely missing. Here, we analyzed the systemic immune response in 3 cohorts of kidney transplanted patients. Using serum proteomics, laboratory values, mass cytometry, histological and clinical parameters, inter-patient heterogeneity was leveraged for multi-omic co-variation analysis. We identified circulating immune modules (CIM) that describe extra-renal signatures of co-regulated plasma proteins. CIM are present in nontransplanted controls, in transplant conditions and during rejection. They are enriched in pathways linked to kidney function, extracellular matrix, signaling, and cellular activation. A complex leukocyte response in the blood during allograft quiescence and rejection is associated with CIM activity and CIM-specific cytokines. CIM activity correlates with kidney function including a 2-month prediction. Together, the data suggest a systemic and multi-layered response of transplant immunity that might be insightful for understanding allograft dysfunction and developing translational biomarkers.Copyright © 2023 Elsevier Inc. All rights reserved.

9 keywords...

hide…