Nützlichkeit verschiedener Crossmatch-Methoden für die Risikostratifizierung bei Patienten mit präformierten donor-spezifischen HLA-Antikörpern vor Lebendnierentransplantation.
Malte Ziemann (Lübeck / DE), Monika Lindemann (Essen / DE), Michael Hallensleben (Hannover / DE), Wolfgang Altermann (Halle / DE), Karina Althaus (Tübingen / DE), Klemens Budde (Berlin / DE), Gunilla Einecke (Hannover / DE), Ute Eisenberger (Essen / DE), Andrea Ender (Stuttgart / DE), Thorsten Feldkamp (Kiel / DE), Florian Grahammer (Hamburg / DE), Martina Guthoff (Tübingen / DE), Christopher Holzmann-Littig (München / DE), Christian Hugo (Dresden / DE), Teresa Kauke (München / DE), Stephan Kemmner (München / DE), Martina Koch (Hamburg / DE; Mainz / DE), Nils Lachmann (Berlin / DE), Matthias Marget (Hamburg / DE), Christian Morath (Heidelberg / DE), Martin Nitschke (Lübeck / DE), Lujtz Renders (München / DE), Sabine Scherer (Heidelberg / DE), Julian Stumpf (Dresden / DE), Vedat Schwenger (Stuttgart / DE), Florian Sommer (Augsburg / DE), Bernd M. Spriewald (Erlangen / DE), Caner Süsal (Heidelberg / DE; Istanbul / TR), Daniel Zecher (Regensburg / DE), Falko M. Heinemann (Essen / DE), Murielle Verboom (Hannover / DE)
Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients is scarce.
DSA-positive living kidney transplant recipients were selected from a multi-center study examining 4233 consecutive renal transplants. Additional seven patients from two further centres were included. Flow cytometric crossmatches (FXM) as well as Luminex-based crossmatches (LXM) and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM, C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples, which could be obtained from 44 donor and recipient pairs from 12 centres. Clinical outcome data and the control group without DSA were compiled from the previous study, and supplemented by data on ten-year death-censored graft survival (10yGS).
Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of ABMR within six months (up to 60% in B-cell FXM+ patients). The incidence of ABMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared to both patients without DSA and to DSA-positive patients with negative FXM.
Especially FXM are useful for risk stratification, as the outcome of DSA-positive FXM- patients is similar to DSA-negative patients, while FXM+ patients have both more ABMR and decreased 10yGS. Due to their lower sensitivity, the significance of LXM, C1qXM and C3dXM would have to be examined in patients with stronger DSA.
The study was supported by a grant of the Stiftung Transfusionsmedizin as well as by free reagents provided by the companies Immucor and ThermoFisher.