The Number of B Cell Epitopes Recognized as a Possible Tool to Improve the Predictive Value of DSA Detected by Flow Beads Assays for Acute Rejection and Graft Loss

Abstract

Although Luminex single antigen beads (SAB) assays allow for the determination of HLA donor-specific antibodies (DSA), the mean fluorescence intensity (MFI) cut-off value that is predictive of acute rejection (AR) and graft loss remains controversial. Here, we retrospectively investigated whether the number of eplets mismatches (MM) targeted by preformed DSA and/or DSA MFI predicted 1-yr AR and acute antibody-mediated rejection (AAMR), as well as death-censored graft loss (DCGL) in a multicenter cohort of 925 kidney transplant recipients. DSA were identified using Luminex SAB assays. Eplet MM were determined by the Matchit software (Gen-Probe Transplant Diagnostics) and HLA Matchmaker (https://www.hlamatchmaker.net). DSA were present in 106 patients before transplantation (11.5%). Median follow-up in these patients was 40 months. One year incidence of AR and AAMR among DSA- patients was 14% and 5.7% respectively while they reached 26.4% and 20.7% in DSA+ patients. Among DSA+ patients, the proportion having at least 2 eplets MM was significantly higher in subgroups with AR and AAMR compared with those free of rejection (AR, 30% vs. 8%, P=0.02; AAMR, 29% vs. 10%, P=0.04). Higher Nº of eplets (≥2) MM was also more prevalent among patients with DCGL (N=12) by comparison with those who kept a functioning graft (N=88) (50% vs. 8.4%, P< 0.001) The cumulative strength of DSA was significantly higher in patients who developed AR compared with those who did not (7784 vs. 3563; P=0.02) and in patients who lost their graft in comparison with those still having a functioning graft (9773 vs. 4169; P=0.04), while a nearly significant trend was observed in patients who experienced AAMR than those who did not (8668 vs. 3908; P=0.07). We conclude that knowledge of the number of eplets MM targeted by DSA may improve the risk stratification of AAMR and DCGL in patients with pretransplant DSA detected by Luminex.