title: De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes.
abstract: Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed-meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1-3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post-first transplant; two post-second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C-peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300-1090); DSA positive 106(34-235) pmol/L [p = 0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p = 0.03).
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A M S
authors.initials: AM
authors.lastname: Brooks
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, National Health Service Blood and Transplant, Newcastle upon Tyne, UK.
authors.forename: V
authors.initials: V
authors.lastname: Carter
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A
authors.initials: A
authors.lastname: Liew
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: H
authors.initials: H
authors.lastname: Marshall
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A
authors.initials: A
authors.lastname: Aldibbiat
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Sheerin
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Manas
authors.affiliation: Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: White
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: J A M
authors.initials: JA
authors.lastname: Shaw
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000209:etiology; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Antibody biology; clinical research/practice; islet isolation; islet transplantation