Circulating donor-specific anti-HLA antibodies (DSA) are associated with allograft failure in solid-organ transplantation. We investigated the pathogenic characteristics of DSA that may improve risk prediction of allograft loss in a population-based study.

We enrolled consecutive patients who received kidney allografts at two Paris centers between 2007 and 2010. Patients were screened for the presence of circulating DSA at the time of transplantation (day-0), at one year and two years after transplantation or during an episode of acute rejection in the first two years after transplantation. We assessed DSA characteristics, including specificity, HLA class, mean fluorescence intensity, C1q-binding capacity, and IgG subclasses at day-0 and at the time of first post-transplant detection.

Of the 858 patients included in the study 88 (10.3%) patients had day-0 DSA and 184 (21.6%) patients were identified with post-transplant DSA. When we considered all immunologic parameters at the time of transplantation, the detection of day-0 DSA was the strongest independent immunologic risk factor of allograft loss (HR=2.7, 95% CI: 1.6-4.6; p<0.001). The post-transplant independent immunologic determinants of allograft loss were the detection of C1q-binding DSA (HR=4.4, 95% CI: 2.2-8.8, p<0.001) and the detection of IgG3-positive DSA (HR=3.5, 95% CI: 1.6-7.4, p=0.001).

We built a multivariate model for allograft loss at the time of transplantation integrating donor age, donor type, cold ischemia time and day-0 DSA. This baseline model showed a moderate discrimination capacity (C-statistic of 0.66). The addition of post-transplant DSA increased significantly the performance of the baseline model (C-statistic of 0.71). The detection of C1q-binding DSA and IgG3-positive DSA further improved the risk prediction of allograft loss: C-statistic, 0.75 (1000 bootstrap mean difference: 0.029, 95% CI: 0.028-0.030) and 0.74 (1000 bootstrap mean difference: 0.022, 95% CI: 0.021-0.023), respectively, and integrated discrimination improvement, 0.07 (p<0.001) and 0.06 (p<0.001), respectively.

Post-transplant serial monitoring of DSA improves risk stratification of kidney allograft loss. The characterization of DSA by complement-binding capacity and IgG3 subclass further improves the performance to predict allograft loss beyond their simple detection.

CITATION INFORMATION: Viglietti D, Loupy A, Bentlejewski C, Legendre C, Glotz D, Zeevi A, Lefaucheur C. Post-Transplant Monitoring of Donor-Specific Anti-HLA Antibodies and Their Characteristics Improves Risk Stratification of Kidney Allograft Loss. Am J Transplant. 2016;16 (suppl 3).

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