Recent interest in characterizing the complement-fixing ability of post-transplant donor specific alloantibodies (DSA) resulted in the enhancement of luminex solid phase alloantibody assays to determine the complement-fixing capacity of DSA. Previous studies have reported a significant correlation of renal biopsy-detected C4d deposition with SAB C1q detection (produced via the classical pathway only). A newly available SAB method detects C3d (produced via the classical, lectin, and alternate pathways) rather than C1q. The purpose of this study was to correlate SAB DSA-associated C3d detection with biopsy evidence of C4d deposition in renal transplant recipients. A cohort of 222 recipients transplanted between 6/2002 and 11/2013 with previously identified post-transplant de novo DSA were retested by SAB C3d assay. A comparison biopsy was available for 187/222 recipients. This 187 patient cohort was 44.8 ± 11.9 (20-74) years old, 64% male (n=119), 36% African-American (n=67), 32% (n=60) sensitized pre-transplant, and 11% (n=21) re-transplant recipients. The median time to first rejection episode experienced by 108/187 (57.8%) recipients was 9.2 months (range 8 days to 6.5 years). The median time of sera testing was 31.4 months post-transplant (range 8 days to 10 years). The biopsy C4d deposition and C3d SAB detection were concordant in 77.5% of cases (145/187), with 81% of cases positive for both (n=118) and 19% negative for both (n=27). In 22.5% of cases the results were discordant (42/187), with 71.4% of cases positive for C4d deposition and negative for SAB C3d detection (n=30) and 28.6% negative for C4d deposition and positive for SAB C3d detection (n=12). The positive predictive value of SAB C3d detection for C4d deposition on biopsy is 91%, the negative predictive value is 47%. Sensitivity of C3d to predict C4d is 79.7%, the specificity is 69.2% with a positive likelihood ratio of 2.6 and negative likelihood ratio of 0.29. We conclude that complement fixation determined by SAB C3d assay correlates well with biopsy evidence of peritubular capillary complement deposition.

CITATION INFORMATION: Pelletier R, Balazs I, Adams P, Steller P, DiPaola N, Rankin L, Diez A, Henry M. Comparison of C4d Deposition in Renal Biopsies with Luminex-Based C3d Single Antigen Bead (SAB) Detection. Am J Transplant. 2016;16 (suppl 3).

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