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

• Published in: Transplantation Vol. 99; no. 1; p. 63
• Main Authors: Touzot, Maxime, Couvrat-Desvergnes, Grégoire, Castagnet, Stéphanie, Cesbron, Anne, Renaudin, Karine, Cantarovich, Diego, Giral, Magali
• Format: Journal Article
• Language: English
• Published: United States 01.01.2015
• Subjects: 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; France
• DOI: 10.1097/tp.0000000000000285

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