EBioMedicine (Jul 2016)

Donor-specific antibodies require preactivated immune system to harm renal transplant

  • Caner Süsal,
  • Bernd Döhler,
  • Andrea Ruhenstroth,
  • Christian Morath,
  • Antonij Slavcev,
  • Thomas Fehr,
  • Eric Wagner,
  • Bernd Krüger,
  • Margaret Rees,
  • Sanja Balen,
  • Stela Živčić-Ćosić,
  • Douglas J. Norman,
  • Dirk Kuypers,
  • Marie-Paule Emonds,
  • Przemyslaw Pisarski,
  • Claudia Bösmüller,
  • Rolf Weimer,
  • Joannis Mytilineos,
  • Sabine Scherer,
  • Thuong H. Tran,
  • Petra Gombos,
  • Peter Schemmer,
  • Martin Zeier,
  • Gerhard Opelz

DOI
https://doi.org/10.1016/j.ebiom.2016.06.006
Journal volume & issue
Vol. 9, no. C
pp. 366 – 371

Abstract

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Background: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. Methods: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. Findings: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1 ± 3.9% and 84.3 ± 2.8%, P = 0.81). A strikingly lower 3-year graft survival rate of 62.1 ± 6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P < 0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. Interpretation: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

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