title: Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure.
abstract: BACKGROUND
  Characteristics of pretransplant antibodies directed at donor human leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist.
  
  
  METHODS
  We prospectively screened pretransplant sera from 543 kidney recipients using single antigen bead assays and identified 154 patients with and 389 without DSA. We investigated the association of DSA features to acute rejection and graft failure.
  
  
  RESULTS
  One-year acute rejection incidence was higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell-mediated rejection (ACR, 5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) of 6,000 or higher (OR, 18; 95% CI, 7.0-47; P < 0.001) and the presence of DSA against both HLA class I and II (OR, 39; 95% CI, 14-106; P < 0.0001) predicted 1-year AMR, independent of other covariates. Calculated panel reactive antibody and a positive flow cytometry cross-match result were associated with AMR by bivariate analysis but neither was an independent predictor in a multivariable regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05-3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher and 2.23 (95% CI, 1.04-4.80; P = 0.04) for class I and II DSA. Prediction of graft failure was not independent of AMR.
  
  
  CONCLUSIONS
  Our study suggests that DSA MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft failure. The elevated risk of graft failure in those with the identified features of DSA is attributable to increased risk of AMR.
authors: 1 Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian-Weill Cornell Medical Center, New York, NY. 2 Department of Transplantation, OSF Saint Francis Medical Center, Peroria, IL. 3 Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 4 Department of Psychiatry and Behavioral Sciences, Stony Brook University, Stony Brook, NY. 5 Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 6 Department of Pathology, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
authors: Dinesh
authors: D
authors: Kannabhiran
authors: John
authors: J
authors: Lee
authors: Joseph E
authors: JE
authors: Schwartz
authors: Rex
authors: R
authors: Friedlander
authors: Meredith
authors: M
authors: Aull
authors: Thangamani
authors: T
authors: Muthukumar
authors: Sean
authors: S
authors: Campbell
authors: David
authors: D
authors: Epstein
authors: Surya V
authors: SV
authors: Seshan
authors: Sandip
authors: S
authors: Kapur
authors: Vijay K
authors: VK
authors: Sharma
authors: Manikkam
authors: M
authors: Suthanthiran
authors: Darshana
authors: D
authors: Dadhania
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D000918:Antibody Specificity; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies
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