title: Antibody-mediated rejection after alemtuzumab induction: incidence, risk factors, and predictors of poor outcome.
abstract: BACKGROUND
  Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied.
  
  
  METHODS
  We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P = 0.0016, 0.001, and 0.012, respectively).
  
  
  RESULTS
  Allograft survival was inferior in the AMR group (70.2%) compared with the nonrejector group (97.0%) (P<0.001). Forty-two of 48 (87.5%) of patients with acute AMR had DSAbs. Patients with CII DSAbs at the time of AMR, whether alone or in combination with CI DSAbs had the worst allograft survival (P = 0.014). Both the mean cumulative and immunodominant mean fluorescence index were higher in those patients who subsequently lost their grafts (P<0.001). Patients with diffuse C4d staining had inferior allograft survival than those with focal C4d or no staining (P = 0.02). There was no significant difference in survival by histological grade but a trend to inferior outcomes in those with vascular involvement (P = 0.06). Those patients who met the full Banff criteria had worse survival than those with suspicion for AMR only (P = 0.04).
  
  
  CONCLUSIONS
  This study identifies patients at risk of graft failure from AMR. These patients may benefit from newer therapeutic strategies including the use of eculizumab or bortezomib.
authors.affiliation: Imperial College Kidney and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Willicombe
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
authors.forename: Paul
authors.initials: P
authors.lastname: Brookes
authors.forename: Jack W
authors.initials: JW
authors.lastname: Galliford
authors.forename: Adam G
authors.initials: AG
authors.lastname: McLean
authors.forename: Anthony
authors.initials: A
authors.lastname: Dorling
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Warrens
authors.forename: Terry H
authors.initials: TH
authors.lastname: Cook
authors.forename: Tom D
authors.initials: TD
authors.lastname: Cairns
authors.forename: David
authors.initials: D
authors.lastname: Taube
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000906:Antibodies / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000074301:CD52 Antigen; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D010446:Peptide Fragments; D000074323:Alemtuzumab; D015935:Complement C4b; C032261:complement C4d