Donor-Specific Antibodies in the Absence of Rejection Are Not a Risk Factor for Allograft Failure

Abstract

Introduction Donor-specific antibodies (DSAs) are considered an important risk factor for graft injury and failure. However, there is limited information on long-term outcomes for kidney transplant recipients with positive DSAs in the absence of rejection on biopsy. Methods We evaluated all patients at the University of Wisconsin who underwent a kidney allograft biopsy between January 1, 2013, and December 31, 2016. All patients with clinical indication or protocol biopsies that were negative for acute rejection and lacked significant acute pathological features were included in the study and divided into 2 groups based on DSAs at the time of biopsy. There were a total of 1102 kidney biopsies during the study period of which 587 fulfilled our selection criteria (DSA+, n = 192, and DSA−, n = 395). The incidence of subsequent rejection and death-censored graft failure (DCGF) were outcomes of interest. Results There was no difference in acute (i + t + v + c4d + ptc + g = 0 in both groups) or chronic (ci + ct + cv + cg = 2.4 ± 2.2 vs. 2.7 ± 2.4; cg = 0.12 ± 0.48 vs. 0.13 ± 0.48) Banff scores in the index biopsy. Patients were followed for a mean of 33.1 ± 16.8 months. Kaplan-Meier analyses demonstrated a higher incidence of DCGF in DSA− group ( n = 83) but this was not observed for subsequent rejection ( n = 76). In multivariate Cox regression analyses, the interval from transplant to biopsy, de novo DSA, and younger age remained independently associated with increased risk of subsequent rejection. Notably, there was no association between subsequent rejection or DSA (pretransplant, de novo , persistant, Class I/II, MFI sum , or MFI max ) and graft failure. Conclusion This study suggests that in the absence of biopsy-proven rejection and acute inflammation, human leukocyte antigen (HLA) DSAs are not associated with increased risk of graft failure.

How Do We Interpret the Presence of Donor-Specific Antibodies When There Is No Rejection?

“…The question of what to do when you have detectable antibody and a negative biopsy is the question underlying the article by Parajuli et al. 4 From 2013 to 2016, they performed 1102 renal allograft biopsies. The study cohort was made up of 587 patients who had no acute changes, of whom 192 had detectable DSA.…”

CYP and SXR gene polymorphisms influence in opposite ways acute rejection rate in pediatric patients with renal transplant

“…In our population, HLA mismatch did not seem to play a significant role in determining acute rejection rate (Table 3). Additionally, HLA mismatch had no significant role in the occurrence of acute rejection in a recent report by Parajuli et al, who analyzed 1102 kidney biopsies and did not find any correlation between the HLA mismatch and the risk of acute rejection [33].…”

A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection

“…All patients included in our study had a negative test for DSA. Screening prospectively for DSA in all patients is not uniformly performed in part due to lack of specificity of DSA to antibody-mediated rejection 24,25 .…”