De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure.
Mittal S., Page SL., Friend PJ., Sharples EJ., Fuggle SV.
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.