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De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes

Lookup NU author(s): Dr Gus Brooks, Dr Aaron Liew, Dr Helen Marshall, Dr Ali Aldibbiat, Professor Neil SheerinORCiD, Professor Derek Manas, Steven White, Professor James Shaw


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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).

Publication metadata

Author(s): Brooks AM, Carter V, Liew A, Marshall H, Aldibbiat A, Sheerin NS, Manas DM, White SA, Shaw JA

Publication type: Article

Publication status: Published

Journal: American Journal of Transplantation

Year: 2015

Online publication date: 30/07/2015

Acceptance date: 23/04/2015

ISSN (print): 1600-6135

ISSN (electronic): 1600-6143

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/ajt.13407

PubMed id: 26227015


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Funder referenceFunder name
Diabetes Foundation
Diabetes Research and Wellness Foundation
Diabetes UK
Juvenile Diabetes Research Foundation
NHS National Commissioning Group
BDA 06/0003362Diabetes UK Grant: Biomedical and Psychosocial Outcomes of Islet Transplantation