title: Donor-specific antibodies require preactivated immune system to harm renal transplant.
abstract: BACKGROUND
  It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect.
  
  
  METHODS
  The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients.
  
  
  RESULTS
  A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative.
  
  
  CONCLUSIONS
  Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany. Electronic address: caner.suesal@med.uni-heidelberg.de.
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruhenstroth
authors.affiliation: Division of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Morath
authors.affiliation: Department of Immunogenetics, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.
authors.forename: Antonij
authors.initials: A
authors.lastname: Slavcev
authors.affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fehr
authors.affiliation: Immunology and Histocompatibility Laboratory, CHU de Québec-Université Laval, Québec, QC, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université Laval, Québec, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Wagner
authors.affiliation: University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Krüger
authors.affiliation: Welsh Transplantation and Immunogenetics Laboratory, Cardiff, United Kingdom.
authors.forename: Margaret
authors.initials: M
authors.lastname: Rees
authors.affiliation: Departments of Transfusion Medicine and Nephrology, Dialysis, Kidney Transplantation, University Hospital Centre, Rijeka, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Balen
authors.affiliation: Departments of Transfusion Medicine and Nephrology, Dialysis, Kidney Transplantation, University Hospital Centre, Rijeka, Croatia.
authors.forename: Stela
authors.initials: S
authors.lastname: Živčić-Ćosić
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Norman
authors.affiliation: Department of Nephrology and Renal Transplantation, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kuypers
authors.affiliation: Blood Transfusion Center, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Emonds
authors.affiliation: Transplantation Surgery, University of Freiburg, Freiburg, Germany.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Pisarski
authors.affiliation: Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bösmüller
authors.affiliation: Department of Internal Medicine, University Clinic of Giessen and Marburg, Giessen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.affiliation: Department of Transplantation Immunology, Institute of Transfusion Medicine, University Clinic Ulm, Ulm, Germany.
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Scherer
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Thuong H
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Gombos
authors.affiliation: Transplantation and General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.affiliation: Division of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.affiliation: Transplantation Immunology, Institute of Immunology, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006085:Graft Survival; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D017730:Ki-1 Antigen / Q000097:blood; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D017730:Ki-1 Antigen
keywords: Donor-specific antibodies; Graft outcome; HLA antibodies; Kidney transplantation; Single antigen bead; sCD30