Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation

Am J Transplant. 2019 Nov;19(11):3100-3113. doi: 10.1111/ajt.15414. Epub 2019 Jun 19.


In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the single-antigen beads assay but complement-dependent cytotoxicity crossmatch-negative. Donor specificity of the preDSA (N = 107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ. Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody-mediated rejection (ABMRh ; 54% and 59% respectively). Patients with preDSA that persisted posttransplant had worse 10-year graft survival compared to resolved DSA and preDSA-negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (hazard ratio [HR] = 8.3) but also in the absence (HR = 4.3) of ABMRh . In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMRh . Even in the absence of antibody-targeting therapy, low median fluorescence intensity DSA and non-DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome.

Keywords: alloantibody; antibody-mediated (ABMR); clinical research/practice; deceased; donors and donation; health services and outcomes research; histocompatibility; kidney transplantation/nephrology; major histocompatibility complex (MHC); organ procurement and allocation; rejection; risk assessment/risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology
  • Graft Rejection / mortality*
  • Graft Rejection / pathology
  • Graft Survival
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / adverse effects*
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Risk Factors
  • Tissue Donors / supply & distribution*


  • HLA Antigens
  • Isoantibodies