title: 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.
  
  
  CONCLUSIONS
  Modulation of DSA at and after treatment of ABMR did not correlate with graft outcome over a 12-month period.
authors.affiliation: 1 Institut National de la Sante Et de la Recherche Medicale INSERM U1064, Nantes, France. 2 Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France. 3 Etablissement Français du Sang (EFS), Laboratoire HLA, Nantes, France. 4 Service D'anatomie Pathologique, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France. 5 Faculté De Médecine, Université de Nantes, Nantes, France. 6 CIC Biotherapy, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Touzot
authors.forename: Grégoire
authors.initials: G
authors.lastname: Couvrat-Desvergnes
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Castagnet
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron
authors.forename: Karine
authors.initials: K
authors.lastname: Renaudin
authors.forename: Diego
authors.initials: D
authors.lastname: Cantarovich
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002648:Child; D005260:Female; D005602:France; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D015415:Biomarkers; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib