Clinical utility of C3d binding donor-specific anti-human leukocyte antigen antibody detection by single antigen beads after kidney transplantationa retrospective study

Development of donor-specific antibodies (DSA) after renal transplantation is known to be associated with worse graft survival, yet determining which specificities in which recipients are the most deleterious remains under investigation. This study evaluated the relationship of the complement binding capacity of post-transplant de novo anti-human leukocyte antigen (HLA) antibodies with subsequent clinical outcome. Stored sera from 265 recipients previously identified as having de novo DSA were retested for DSA and their C3d binding capacity using Luminex-based solid-phase assays. Most recipients had anti-HLA class II-reactive DSA (class I = 12.5%, class II = 68.7%, class I and class II = 18.9%). The recipients that had C3d binding DSA (67.5%) had a significantly higher incidence of antibody-mediated rejection and any rejection. They also had significantly lower kidney survival, with the lowest survival in those that had both anti-HLA class I and class II C3d binding DSA. Concurrent biopsy comparison revealed a 96.2% positive predictive value and 47.4% negative predictive value for C4d peritubular capillary (Ptc) deposition. Anti-HLA class I and class II C3d binding DSA carried a twofold and 1.5-fold increased risk of kidney loss, respectively, in multivariate analysis.