title: De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure.
abstract: This study assesses the role of posttransplant HLA antibody monitoring in the surveillance of pancreas transplant recipients. Four hundred thirty-three pancreas transplants were performed at the Oxford Transplant Centre 2006-2011 (317 simultaneous pancreas kidney [SPK] and 116 isolated pancreas [IP]). HLA antibody monitoring was performed at 0, 6 and 12 months and annually and during clinical events. There was no association between pancreas graft failure and recipient or donor characteristics. Posttransplant antibody status, available for 354 (81.8%) of recipients, demonstrated that 141 (39.8%) developed de novo HLA antibodies, of which 52 (36.9%) were de novo donor-specific HLA antibodies (DSA) (34 SPK, 18 IP). The development of antibodies to donor HLA, but not to nondonor HLA, was significantly associated with poorer graft outcomes, with 1- and 3-year graft survival inferior in SPK recipients (85.2% vs. 93.5%; 71.8% vs. 90.3%, respectively; log-rank p = 0.002), and particularly in IP recipients (50.0% vs. 82.9%; 16.7 vs. 79.4%, respectively; log-rank p = 0.001). In a multivariate analysis, development of de novo DSA emerged as a strong independent predictor of pancreas graft failure (hazard ratio 4.66, p < 0.001). This is the largest study to examine de novo HLA antibodies following pancreas transplantation and clearly defines a high-risk group in need of specific intervention.
authors.affiliation: Oxford Transplant Centre, Oxford, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mittal
authors.forename: S L
authors.initials: SL
authors.lastname: Page
authors.forename: P J
authors.initials: PJ
authors.lastname: Friend
authors.forename: E J
authors.initials: EJ
authors.lastname: Sharples
authors.forename: S V
authors.initials: SV
authors.lastname: Fuggle
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D016035:Pancreas Transplantation / Q000009:adverse effects*; D010182:Pancreatic Diseases / Q000150:complications / Q000601:surgery; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies
keywords: Antibodies; pancreas transplant; risk factors; survival; transplant outcome; type 1 diabetes