title: Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing.
abstract: BACKGROUND
  The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure.
  
  
  METHODS
  We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts.
  
  
  RESULTS
  The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001).
  
  
  CONCLUSIONS
  Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.
authors.affiliation: 1 Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. 2 Department of Nephrology, University of Heidelberg, Heidelberg, Germany. 3 Department of Transplantation and General Surgery, University of Heidelberg, Heidelberg, Germany. 4 Immunology and Histocompatibility Laboratory, CHU de Quebec, Quebec, QC, Canada. 5 Department of Microbiology, Infectious Diseases and Immunology, Laval University, Quebec, QC, Canada. 6 Division of Nephrology, University Hospital Zurich, Switzerland. 7 Departments of Nephrology, Dialysis, Kidney Transplantation and Transfusion Medicine, University Hospital Centre, Rijeka, Croatia. 8 Department of Internal Medicine, University Clinic of Giessen and Marburg, Campus Giessen, Giessen, Germany. 9 Department of Immunogenetics, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. 10 Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria. 11 Oregon Health and Science University, Portland, OR.
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
authors.forename: Daniel
authors.initials: D
authors.lastname: Wettstein
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
authors.forename: Christian
authors.initials: C
authors.lastname: Morath
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruhenstroth
authors.forename: Sabine
authors.initials: S
authors.lastname: Scherer
authors.forename: Thuong H
authors.initials: TH
authors.lastname: Tran
authors.forename: Petra
authors.initials: P
authors.lastname: Gombos
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.forename: Eric
authors.initials: E
authors.lastname: Wagner
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
authors.forename: Stela
authors.initials: S
authors.lastname: Živčić-Ćosić
authors.forename: Sanja
authors.initials: S
authors.lastname: Balen
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.forename: Antonij
authors.initials: A
authors.lastname: Slavcev
authors.forename: Claudia
authors.initials: C
authors.lastname: Bösmüller
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Norman
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015922:Complement C1q / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D015922:Complement C1q