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

Targeting peritransplant inflammation via tumor necrosis factor alpha blockade failed to improve kidney transplantation outcomes in the CTOT-19 trial that tested infliximab (IFX) induction. As natural antibodies (nAbs) to cardiolipin and phosphatidylethanolamine promote graft injury, we hypothesized that CTOT-19 outcomes were confounded by nAb levels. Pretransplant plasma anticardiolipin (aCL) and antiphosphatidylethanolamine (aPE) immunoglobulin M/immunoglobulin G (IgM/IgG) were measured in 177 CTOT-19 subjects and analyzed in relation to delayed graft function (DGF), 2-year estimated glomerular filtration rate, and infection. Bayesian modeling with a nonlinear 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 (odds ration [OR] at the fifth percentile, 0.13; 95% credible interval (95% CrI), 0.03-0.49) but increases risk at the 95th percentile of aCL IgG levels (OR, 6.24; 95% CrI, 1.38-30.32). In patients with aCL IgG below the median, IFX has a positive indirect effect on the estimated glomerular filtration rate via reducing DGF rates. Finally, IFX increases infection risk in patients with low aPE IgG (OR at the fifth percentile, 3.12; 95% CrI, 1.11-9.08). This analysis identifies a subset of CTOT-19 subjects who likely benefit from IFX and suggests pretransplant nAb levels may serve as biomarkers for response to early posttransplant anti-inflammatory therapies.