De Novo Donor‐Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes. Issue 12 (30th July 2015)

• Record Type: Journal Article
• Authors: Brooks, A. M. S.; Carter, V.; Liew, A.; Marshall, H.; Aldibbiat, A.; Sheerin, N. S.; Manas, D. M.; White, S. A.; Shaw, J. A. M.
• Is Part Of: American journal of transplantation. Volume 15:Issue 12(2015:Dec.)
• Page Start: 3239
• Page End: 3246
• Publication Date: 2015-07-30
• Subjects: Antibody biology -- clinical research/practice -- islet isolation -- islet transplantation; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13407
• Languages: English
• ISSNs: 1600-6135

Abstract

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). Abstract : Through prospective follow up of a single‐center cohort of pancreatic islet transplant recipients, the authors demonstrate that development of de novo donor‐specific antibodies occurs rapidly after the sensitizing transplant and is absolutely associated with graft loss at 12 months.