Impact of donor-specific antibodies on chronic rejection occurrence and graft loss in renal transplantation: posttransplant analysis using flow cytometric techniques

Transplantation. 2001 Apr 27;71(8):1106-12. doi: 10.1097/00007890-200104270-00017.


Background: Improvements in immunosuppressive therapy have greatly reduced acute rejection (ARj) episodes, ensuring better short-term graft outcome, but have not modified long-term survival in renal transplantation. It is now well accepted that chronic rejection (CRj) can be determined by both immune and/or nonimmune mechanisms. The aim of this study was to evaluate the importance of the posttransplant humoral immune response towards mismatched HLA graft antigens in CRj occurrence and graft outcome.

Methods: Serum samples from 120 nonpresensitized renal transplant recipients were prospectively screened for 1 year after surgery by means of flow cytometry cross-match (FCXM) and FlowPRA beads (microbeads coated with purified HLA class I and class II antigens) assays. All transplants were followed-up for 2 years or until graft removal.

Results: FCXM monitoring identified donor-specific antibodies (DS-Abs) in 29 (24.2%) of 120 transplanted patients. Correlation with clinical data highlighted a higher incidence of ARj in DS-Abs-positive patients compared to negative patients (62% vs. 13%, P<0.00001). Furthermore, graft failure occurred more frequently among FCXM-positive patients than among negative patients (34% vs. 1%, P<0.00001). The deleterious effect of DS-Abs on graft function was confirmed by serum creatinine levels 2 years after transplantation. These were in fact higher in subjects producing DS-Abs than in subjects with only ARj (mean creatinine: 2.5+/-1.3 mg/dL vs.1.7+/-0.5 mg/dL, P=0.04). FlowPRA analysis of DS-Ab HLA specificity highlighted the presence of anti-HLA class I antibodies in 85% of FCXM-positive patients, who also presented with a higher incidence of HLA-B mismatches than FCXM-negative patients (1.23+/-0.66 vs. 0.92+/-0.59, P=0.02).

Conclusions: Flow cytometric techniques are precious tools for investigating the activation of the humoral response against HLA antigens of the graft in renal transplantation. DS-Abs production has a worse impact on organ function and survival than ARj episodes. These findings represent further proof of the threat posed by DS-Abs on long-term graft function and draw attention to the need for a specific immunosuppressive therapy aimed at counteracting the different kinds of immune activation toward graft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Creatinine / blood
  • Female
  • Flow Cytometry / methods
  • Graft Rejection / epidemiology*
  • Graft Rejection / immunology
  • HLA-A Antigens / immunology
  • HLA-B Antigens / immunology
  • HLA-DR Antigens / immunology
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / immunology*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / physiology
  • Male
  • Reoperation
  • Treatment Failure
  • Treatment Outcome


  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens
  • Isoantibodies
  • Creatinine