Pretransplant natural antibody levels identify a subset of deceased donor kidney transplant recipients that benefit from infliximab induction

Vojtech Petr; Filip Tichanek; Samuel L Liu; Felix Poppelaars; Brandon Renner; Jennifer Laskowski; Shrey Purohit; Ming Zhao; Diana Jalal; Peter S Heeger; Joshua M Thurman

doi:10.1016/j.ajt.2025.06.003

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Pretransplant natural antibody levels identify a subset of deceased donor kidney transplant recipients that benefit from infliximab induction

Journal article

Peer reviewed

Pretransplant natural antibody levels identify a subset of deceased donor kidney transplant recipients that benefit from infliximab induction

Vojtech Petr, Filip Tichanek, Samuel L Liu, Felix Poppelaars, Brandon Renner, Jennifer Laskowski, Shrey Purohit, Ming Zhao, Diana Jalal, Peter S Heeger, …

American journal of transplantation, Vol.25(10), pp.2173-2181

10/2025

DOI: 10.1016/j.ajt.2025.06.003

PMID: 40484132

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Abstract

Targeting peri-transplant inflammation via TNFα blockade failed to improve kidney transplantation outcomes in the CTOT19 trial that tested infliximab (IFX) induction. As natural antibodies (nAbs) to cardiolipin (CL) and phosphatidylethanolamine (PE) promote graft injury, we hypothesized that CTOT19 outcomes were confounded by nAb levels. Pretransplant plasma aCL and aPE IgM/IgG were measured in 177 CTOT19 subjects and analyzed in relation to delayed graft function (DGF), 2-year estimated glomerular filtration rate (eGFR), and infection. Bayesian modeling with a non-linear treatment-antibody interaction estimated that the IFX effects depend on aCL IgG/IgM and aPE IgG. In patients with low aCL IgG, IFX reduces DGF risk (OR at 5 percentile: 0.13; 95% Credible interval (95%CrI): 0.03 to 0.49) but increases risk at the 95 percentile of aCL IgG levels (OR: 6.24; 95%CrI: 1.38 to 30.32). In patients with aCL IgG below the median, IFX has a positive indirect effect on eGFR via reducing DGF rates. Finally, IFX increases infection risk in patients with low aPE IgG (OR at 5th percentile: 3.12; 95%CrI: 1.11 to 9.08). This analysis identifies a subset of CTOT19 subjects who likely benefit from IFX and suggests pretransplant nAb levels may serve as biomarkers for response to early posttransplant anti-inflammatory therapies.

TNF-alpha

infliximab

Delayed graft function

natural antibodies

Details

Title: Subtitle: Pretransplant natural antibody levels identify a subset of deceased donor kidney transplant recipients that benefit from infliximab induction
Creators: Vojtech Petr - University of Colorado Anschutz Medical Campus
Filip Tichanek - Institute of Clinical and Experimental Medicine
Samuel L Liu - Northwestern University
Felix Poppelaars - University of Colorado Anschutz Medical Campus
Brandon Renner - University of Colorado Anschutz Medical Campus
Jennifer Laskowski - University of Colorado Anschutz Medical Campus
Shrey Purohit - University of Colorado Anschutz Medical Campus
Ming Zhao - Northwestern University
Diana Jalal - Iowa City VA Health Care System
Peter S Heeger - Cedars-Sinai Medical Center
Joshua M Thurman - University of Colorado Anschutz Medical Campus
Resource Type: Journal article
Publication Details: American journal of transplantation, Vol.25(10), pp.2173-2181
DOI: 10.1016/j.ajt.2025.06.003
PMID: 40484132
NLM abbreviation: Am J Transplant
ISSN: 1600-6143
eISSN: 1600-6143
Publisher: ELSEVIER SCIENCE INC
Grant note: National Institutes of Health: R01DK076690, R01DK113586, R01DK138960, R01DK125823, 1R21AI171491, U01 AI63594, U01 AI170424
This work was supported by National Institutes of Health Grants R01DK076690, R01DK113586, R01DK138960, and R01DK125823 awarded to Joshua Thurman; 1R21AI171491 awarded to Ming Zhao; and U01 AI63594 and U01 AI170424 awarded to Peter Heeger.
Language: English
Electronic publication date: 06/06/2025
Date published: 10/2025
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984829018902771

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