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. TranPetra Gombos, Peter Schemmer, Martin Zeier, Gerhard Opelz

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)366-371
Number of pages6
JournalEBioMedicine
Volume9
DOIs
StatePublished - 2016

Keywords

  • Donor-specific antibodies
  • Graft outcome
  • HLA antibodies
  • Kidney transplantation
  • Single antigen bead
  • sCD30

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Süsal, C., Döhler, B., Ruhenstroth, A., Morath, C., Slavcev, A., Fehr, T., Wagner, E., Krüger, B., Rees, M., Balen, S., Živčić-Ćosić, S., Norman, D. J., Kuypers, D., Emonds, M. P., Pisarski, P., Bösmüller, C., Weimer, R., Mytilineos, J., Scherer, S., ... Opelz, G. (2016). Donor-specific antibodies require preactivated immune system to harm renal transplant. EBioMedicine, 9, 366-371. https://doi.org/10.1016/j.ebiom.2016.06.006