title: Clinically-relevant threshold of preformed donor-specific anti-HLA antibodies in kidney transplantation.
abstract: BACKGROUND
  Pretransplant anti-HLA donor-specific antibodies (DSA) are recognized as a risk factor for acute antibody-mediated rejection (AMR) in kidney transplantation. The predictive value of C4d-fixing capability by DSA or of IgG DSA subclasses for acute AMR in the pretransplant setting has been recently studied. In addition DSA strength assessed by mean fluorescence intensity (MFI) may improve risk stratification. We aimed to analyze the relevance of preformed DSA and of DSA MFI values.
  
  
  METHODS
  280 consecutive patients with negative complement-dependent cytotoxicity crossmatches received a kidney transplant between 01/2008 and 03/2014. Sera were screened for the presence of DSA with a solid-phase assays on a Luminex flow analyzer, and the results were correlated with biopsy-proven acute AMR in the first year and survival.
  
  
  RESULTS
  Pretransplant anti-HLA antibodies were present in 72 patients (25.7%) and 24 (8.6%) had DSA. There were 46 (16.4%) acute rejection episodes, 32 (11.4%) being cellular and 14 (5.0%) AMR. The incidence of acute AMR was higher in patients with pretransplant DSA (41.7%) than in those without (1.6%) (p<0.001). The median cumulative MFI (cMFI) of the group DSA+/AMR+ was 5680 vs 2208 in DSA+/AMR- (p=0.058). With univariate logistic regression a threshold value of 5280 cMFI was predictive for acute AMR. DSA cMFI's ability to predict AMR was also explored by ROC analysis. AUC was 0.728 and the best threshold was a cMFI of 4340. Importantly pretransplant DSA>5280 cMFI had a detrimental effect on 5-year graft survival.
  
  
  CONCLUSIONS
  Preformed DSA cMFI values were clinically-relevant for the prediction of acute AMR and graft survival in kidney transplantation. A threshold of 4300-5300 cMFI was a significant outcome predictor.
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland. Electronic address: igor.salvade@chuv.ch.
authors.forename: Igor
authors.initials: I
authors.lastname: Salvadé
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Aubert
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Venetz
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Dela
authors.initials: D
authors.lastname: Golshayan
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Saouli
authors.affiliation: Service of Visceral Surgery, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: Matter
authors.affiliation: Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rotman
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.affiliation: Transplantation Center and Service of Immunology and Allergy, Lausanne University Hospital, 1011 Lausanne, Switzerland. Electronic address: manuel.pascual@chuv.ch.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing / Q000592:standards*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012015:Reference Standards; D012306:Risk
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Acute AMR; DSA; Kidney transplantation; cMFI