Differential Modulation of Donor-Specific Antibodies After B-Cell Depleting Therapies to Cure Chronic Antibody Mediated Rejection

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.