title: Donor specific antibodies before and after kidney transplant: the University of Colorado Experience.
abstract: We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.22), although acute rejection occurred earlier in the DSA+ group. De novo DSA was detected in 65 of 261 patients (27%). All DSA was detected within the first posttransplant year. While acute rejection was more likely in patients with de novo DSA (29% versus 9.5% in those with no DSA), prospective DSA screening failed to predict this outcome as DSA was detected at the time of or after a rejection episode in 16 of 19 patients with both DSA and acute rejection. Two-year estimated graft survival was significantly worse in patients with versus without DSA, but was identical when removing patients with a prior acute rejection episode from the analysis. We have used a protocol of high dose (5 gm/kg) intravenous immunoglobulin infused over the course of 6 months in patients with DSA and either chronic graft dysfunction or following a recent acute antibody mediated rejection (AMR) episode. DSA MFI was reduced by 18% from the time of initiation to last follow up. This effect was largely due to reductions in class I DSA (-37%) and DSA in patients with a recent acute AMR (-51.5%), with a minimal effect on class II DSA and DSA in patients with chronic graft dysfunction. Despite treatment directed at antibody-producing plasma cells, antibody levels either persisted or worsened with no improvement in graft function. Overall, DSA is more amendable to treatment when associated with a recent acute rejection event.
authors.forename: James E
authors.initials: JE
authors.lastname: Cooper
authors.forename: Jane
authors.initials: J
authors.lastname: Gralla
authors.forename: Oluwafisayo
authors.initials: O
authors.lastname: Adebiyi
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Wiseman
authors.forename: Laurence
authors.initials: L
authors.lastname: Chan
mesh_terms: D000208:Acute Disease; D003120:Colorado; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006785:Hospitals, University; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D011184:Postoperative Period; D057234:Preoperative Period; D011446:Prospective Studies; D016036:Seroepidemiologic Studies; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies