Donor-specific HLA antibodies (DSA) are associated with poorer outcomes in kidney transplantation, however the role of DSA in pancreas transplantation is less well known. This study aims to assess the role of routine serial HLA antibody monitoring in identifying grafts at risk of failure after pancreas transplantation.

The patient cohort included recipients of pancreas transplants performed at our centre between 2006 and 2011; 317 simultaneous pancreas kidney (SPK) and 126 isolated pancreas (IP) transplants. Prospective serial HLA antibody screening was performed by Luminex technology pre- transplant, at 0, 6, 12 and 24 months post-operativey and at the time of clinical events. Samples were screened for the presence of antibodies using LABScreen® Mixed kits and antibody specification performed using LABScreenPRA® and Single Antigen beads. Demographic and graft outcome data was collected, including rejection episodes and graft failures (return to insulin-dependence). The antibody monitoring results were analyzed for associations to pancreas graft outcomes.

Pre-transplant HLA antibody screening was performed routinely on all 433 patients and 354 (81.8%) had post-transplant HLA antibody monitoring. There was no association between pancreas graft failure and recipient or donor characteristics, including pre-transplant sensitisation status, HLA mismatch (0-6) or DR mismatch (0-2). 141/354 (39.3%) recipients developed de novo HLA antibodies and 54/354 (15.3%) developed de novo DSA, of which 34 were SPK and 20 IP transplants. There was no association between the development of non-donor specific HLA antibodies and graft failure, however, the development of DSA was significantly associated with poorer graft outcomes for both SPK and IP transplants. Inferior one and three year graft survival rates were achieved in SPK recipients who developed de novo DSA compared to those who did not (1 year graft survival, 78.3% vs. 94.7%; 3 year survival 63.6% vs. 92.5%; log rank p=0.001), but the differences were more pronounced in the IP group (1 year graft survival, 50.0% vs. 89.4%; 3 year survival 14.3% vs. 85.8%; log rank p=0.001).

This is the largest study to date to examine the association between de novo HLA antibodies following pancreas transplant and graft outcomes, and clearly demonstrates a strong association between development of DSA and graft failure particularly in the IP group. These high risk patients are a logical target group for novel immunosuppressive interventions.

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