Differential modulation of donor-specific antibodies after B-cell depleting therapies to cure chronic antibody mediated rejection

Transplantation. 2015 Jan;99(1):63-8. doi: 10.1097/TP.0000000000000285.

Abstract

Background: Donor-specific antibodies (DSA) are considered as reliable biomarkers for antibody-mediated rejection (ABMR) diagnosis. However, it is unclear whether DSA monitoring is necessary and could predict graft outcome after antirejection treatment.

Methods: We analyzed 28 non-sensitized kidney transplant patients with ABMR associated with de novo anti-human leukocyte antigen (HLA) DSA. Donor-specific antibody levels were measured by single antigen bead assays 12 months after antirejection therapy onset. Patients were placed in three groups according to their antirejection treatment: group I (n = 10), plasma exchange-Rituximab; group II (n = 8), Bortezomib; and group III (n = 10), optimization of maintenance immunosuppression. Half of the patients in group I demonstrated concomitant acute cellular rejection (ACR+).

Results: De novo DSA were mainly anti-DQ (60%). Anti-class I and anti-DR DSA disappeared after treatment in group I and remained negative during follow-up, whereas anti-DQ DSA persisted without any modulation. In contrast, class I-II HLA-DSA mean fluorescence intensity remained unchanged in groups II and III.Graft loss was observed in 80% and 20% of patients from group I (ACR+) and group III, respectively. One year after the ABMR treatment, a 16-mL/min decline in estimated glomerular filtration rate was observed in patients from group I (ACR-) and group III. Group II showed better outcomes with a mean estimated glomerular filtration rate decline of 6.4 mL/min.

Conclusion: Modulation of DSA at and after treatment of ABMR did not correlate with graft outcome over a 12-month period.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Autoantibodies / blood*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Biomarkers / blood
  • Biopsy
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Child
  • Female
  • France
  • Graft Rejection / blood
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology
  • Graft Rejection / therapy*
  • Graft Survival / drug effects
  • HLA Antigens / immunology*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Plasmapheresis*
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Retrospective Studies
  • Rituximab
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Biomarkers
  • Boronic Acids
  • HLA Antigens
  • Immunosuppressive Agents
  • Pyrazines
  • Rituximab
  • Bortezomib