title: De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection.
abstract: BACKGROUND
  Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection.
  
  
  METHODS
  We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients.
  
  
  RESULTS
  Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 ± 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 ± 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores.
  
  
  CONCLUSIONS
  Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.
authors.affiliation: 1 INSERM U1149, Paris, France. 2 Université Paris 7-Denis Diderot, Paris, France. 3 Laboratoire Régional d'Histocompatibilité, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France. 4 Laboratoire D'Anatomie Pathologique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 5 Service de Néphrologie et Transplantation Adulte, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 6 Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 7 RTRS Centaure, Labex Transplantex, Paris, France. 8 Laboratoire D'Immunologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 9 Service D'Urologie, HEGP-Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 10 INSERM U1151, Paris, France.
authors.forename: Jonathan-Maurice
authors.initials: JM
authors.lastname: Chemouny
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Marie-Alexandra
authors.initials: MA
authors.lastname: Alyanakian
authors.forename: Xavier
authors.initials: X
authors.lastname: Lebreton
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.forename: Nathan
authors.initials: N
authors.lastname: Pinheiro
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loupy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Van Huyen
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Timsit
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Dany
authors.initials: D
authors.lastname: Anglicheau
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D003404:Creatinine