Does a Useful Test Exist to Properly Evaluate the Pathogenicity of Donor-specific Antibodies? Lessons From a Comprehensive Analysis in a Well-studied Single-center Kidney Transplant Cohort

Transplantation. 2020 Oct;104(10):2148-2157. doi: 10.1097/TP.0000000000003080.

Abstract

Background: Donor-specific antibodies (DSA) play a major role in antibody-mediated rejection (AMR) and graft dysfunction. However, the clinical relevance of complement-binding anti-HLA antibodies remains unclear.

Methods: Here, we analyzed DSA detected in the serum (sDSA) using single antigen bead, C1q, and C3d assays combined with the study of intragraft DSA (gDSA) in 86 patients who had DSA and underwent a kidney biopsy for cause (n = 58) or without evidence of kidney dysfunction (n = 28). DSA characteristics were collected and related to the presence of AMR, graft histological features, and allograft survival.

Results: Forty-five patients (52%) had C1q DSA, and 42 (51%) had C3d DSA. Allograft biopsies revealed AMR in 63 cases (73%), regardless of kidney function. gDSA were identified in 74% of biopsies. We observed a strong correlation among single antigen bead mean fluorescence intensity and complement assays positivity, presence of gDSA, and AMR occurrence.

Conclusions: Complement-binding DSA per se were not significantly associated with allograft survival in the entire study sample. Finally, gDSA predicted subsequent graft loss in patients who showed a stable renal function at the day of biopsy. Our data suggest that DSA mean fluorescence intensity and presence of gDSA might provide prognostic information during posttransplant monitoring.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Biopsy
  • Child
  • Child, Preschool
  • Complement C1q / immunology
  • Complement C3d / immunology
  • Complement Fixation Tests*
  • Female
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Graft Survival
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Monitoring, Immunologic*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • HLA Antigens
  • Isoantibodies
  • Complement C1q
  • Complement C3d