A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

Abstract

SummaryAcute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA<30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity=76.5%, specificity= 88.9%). The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information.

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large, multi‐centre study

“…Leucocyte subsets were determined based on the epigenetic quantification, as described before [15,16]. Screening of serum antibody binding profile (SAB) was performed employing HLA‐1 mixed antigen bead assay; the raw mean fluorescence intensity for each bead was employed for prediction [17]. The urinary metabolomics spectrum was measured by nuclear magnetic resonance (NMR) spectroscopy at numares AG (Regensburg, Germany).…”

Early prediction of renal graft function: Analysis of a multi-centre, multi-level data set

“…[25–28] Serum antibodies (SAB) were screened employing HLA-1 mixed antigen bead assay; the raw mean fluorescence intensity for each bead was employed for prediction. [10] The urinary metabolomics spectrum was determined employing nuclear magnetic resonance (NMR), which was binned and normalized to facilitate the analysis. Finally, while viral loads were monitored by qPCR as described before, other clinical data were measured de-centrally and provided by the transplantation centres.…”

“…The most commonly used end-point for risk assessment models is the incidence of acute rejection. [10–14] However, acute rejection occurs rather infrequently in renal transplantation and treatments against acute rejection are reasonably effective. [1,15–17] The estimated Glomerular Filtration Rate (eGFR) could therefore offer a more appropriate end-point.…”