Solid phase detection of C4d-fixing HLA antibodies to predict rejection in high immunological risk kidney transplant recipients

Gregor Bartel, Markus Wahrmann, Elisabeth Schwaiger, Željko Kikić, Christine Winzer, Walter H Hörl, Ferdinand Mühlbacher, Matthias Hoke, Gerhard J Zlabinger, Heinz Regele, Georg A Böhmig
Transplant International 2013, 26 (2): 121-30
Protocols for recipient desensitization may allow for successful kidney transplantation across major immunological barriers. Desensitized recipients, however, still face a considerable risk of antibody-mediated rejection (AMR), which underscores the need for risk stratification tools to individually tailor treatment. Here, we investigated whether solid phase detection of complement-fixing donor-specific antibodies (DSA) has the potential to improve AMR prediction in high-risk transplants. The study included 68 sensitized recipients of deceased donor kidney allografts who underwent peritransplant immunoadsorption for alloantibody depletion (median cytotoxic panel reactivity: 73%; crossmatch conversion: n = 21). Pre and post-transplant sera were subjected to detection of DSA-triggered C4d deposition ([C4d]DSA) applying single-antigen bead (SAB) technology. While standard crossmatch and [IgG]SAB testing failed to predict outcomes in our desensitized patients, detection of preformed [C4d]DSA (n = 44) was tightly associated with C4d-positive AMR [36% vs. 8%, P = 0.01; binary logistic regression: odds ratio: 10.1 (95% confidence interval: 1.6-64.2), P = 0.01]. Moreover, long-term death-censored graft survival tended to be worse among [C4d]DSA-positive recipients (P = 0.07). There were no associations with C4d-negative AMR or cellular rejection. [C4d]DSA detected 6 months post-transplantation were not related to clinical outcomes. Our data suggest that pretransplant SAB-based detection of complement-fixing DSA may be a valuable tool for risk stratification.

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