Pretransplant human leukocyte antigen antibodies detected by single-antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor-specific antibodies

Abstract

SUMMARYClinical relevance of ELISA-and single-antigen bead assay (SAB)-detected pretransplant HLA antibodies (SAB-HLA-Ab) for kidney graft survival was evaluated retrospectively in 197 patients transplanted between 2002 and 2009 at the University Clinic Frankfurt. Having adjusted for retransplantation and delayed graft function, a significantly increased risk for death-censored graft loss was found in patients with pretransplant SAB-HLA-Ab [HR: 4.46; 95% confidence interval (CI): 1.47-13.48; P = 0.008]. The risk for increased graft loss was also significant in patients with pretransplant SAB-HLA-Ab but without SAB-detected donor-specific Ab (SAB-DSA) (HR: 4.91; 95% CI of 1.43-16.991; P = 0.012). ELISA was not sufficient to identify pretransplant immunized patients with an increased risk for graft loss. In immunized patients, graft loss was predominantly present in patients who received transplants with a mismatch on the HLA-DR locus. In conclusion, even if our study is limited due to small sample size, the results show an increased risk for long-term graft loss in patients with pretransplant SAB-HLA, even in the absence of DSA. SAB-HLA-Ab-positive patients, being negative in ELISA or CDC assay, might profit from a well-HLA-DR-matched graft and intensified immunosuppression. Transplant International 2016; 29: 988-998

Tracing clinically relevant HLA antibodies prior to kidney transplantation: Commentary on “Pre-transplant HLA antibodies detected by single antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor specific antibodi

“…Richter et al . could nicely demonstrate that ELISA HLAab revealed no decreased graft survival probability but patients received intensified immunosuppression with antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. Thus, it can be speculated that patients at risk with pretransplant HLAab as detected by SAB could benefit from intensified immunosuppressive regimens.…”

“…As Richter et al . clearly show in their supplemental figures, ELISA revealed a pronounced deficiency to detect HLA‐C and DQ antibodies. More strikingly, ELISA even failed to detect certain HLA‐A and B specificities commonly assigned using the SAB assay.…”

“…In their article, Richter et al . could demonstrate that preformed DSA as detected by SAB exceeding 3000 mean fluorescence intensity (MFI) units represent an independent risk factor for allograft survival. As known from several post‐transplant studies also non‐DSA (NDSA) revealed a negative impact on graft survival which could also be confirmed here in the pretransplant setting.…”

“…Richter et al . nicely elaborated that patients preimmunized with SAB HLAab could potentially benefit from well‐matched kidney allografts. Especially, the importance of matching for HLA‐DR was eminent.…”

“…In this issue, the article by Richter et al . focused retrospectively on the comparison between ELISA and SAB assays to detect clinically relevant HLAab pretransplant. Briefly, the authors analyzed the 5‐year death‐censored allograft survival on a total of 197 kidney transplants performed with a negative CDC cross‐match under consideration of unacceptable HLA class I antigens as defined by ELISA and CDC.…”