Abstract
Aim Sensitized heart transplant candidates are evaluated for donor specific HLA antibody (DSA) by Luminex single antigen bead (SAB) testing to assess donor suitability and predict a positive complement dependent cytotoxicity (CDC) crossmatch (XM) by virtual XM (VXM). However, SAB testing imperfectly correlates with VXM, and antibody thresholds for XM prediction are center-specific. A novel Luminex SAB-based assay detecting C1q-binding HLA antibodies adds functional data to SAB testing, but the relationship between SAB strength and C1q positivity is unclear. In this retrospective study, we examine the relationship between HLA antibody titer and complement-binding ability in cardiac allograft recipients and correlate C1q DSA to antibody-mediated rejection (AMR). Methods We identified 15 sensitized pediatric and adult heart recipients with a calculated panel reactive antibody >50%. Sera were tested by conventional SAB antibody testing using undiluted or 1:16 diluted sera and were compared to C1q results. Pre- and post-transplant DSA by both methods were correlated with XM and early AMR. Results In 9 samples, individual Class I antibodies measured by SAB testing in undiluted sera correlated poorly with C1q reactivity (R 2 = 0.07). In contrast, using sera diluted 1:16, conventional SAB results correlated better with C1q testing ( R 2 = 0.73). Receiver operator characteristic curve analysis also showed superior area under the curve (AUC) for predicting C1q positive results in sera diluted 1:16 than in undiluted sera (AUC = 0.99 vs 0.82). Low MFI by conventional SAB testing in alleles with high C1q MFI increased upon dilution or heat-treating sera and correlated with C1q results. Clinically, in 13 recipients C1q DSA predicted CDC-XM positivity and early AMR (positive predictive value (PV) 87.5%; negative PV 100%). Conclusions In conclusion, SAB titer correlated with and predicted C1q reactivity. The risk for positive crossmatch and early AMR in sensitized heart recipients strongly correlated with C1q binding DSA.
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