Findings

CTS Pre-Transplant Findings

With the collaboration of 29 centers, it was possible to show in a first study of 3,900 kidney transplants that pretransplant determination of sCD30, especially in combination with HLA antibodies, is a good indicator for estimating the risk of graft rejection (1). In a more recent multi-center study we could extend this finding to donor-specific HLA antibodies (DSA) detected by single antigen bead technology (SAB). In presensitized patients with cytotoxic or ELISA-reactive HLA antibodies, pretransplant DSA influenced graft survival; however, only if the patients were, in addition, positive also for sCD30 (2). Graft survival was not impaired in DSA-positive presensitized patients with low sCD30 indicating that an activated immune system and T cell help is a prerequisite for pretransplant DSA to exert their harmful effects.
In our local cohort of immunologically high-risk patients we could demonstrate that, in the absence of sCD30, pretransplant DSA disappear after transplantation in many patients, and high-risk patients with pretransplant positivity of the activation marker sCD30 are at a seven times higher risk of graft loss than sCD30-negative recipients (3). Our data suggest that patients positive for both pretransplant DSA and sCD30 require special measures, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement activating (2,3).
In a survey of more than 160,000 patients transplanted between 1982 and 2002 we made the surprising observation that high pretransplant lymphocytotoxic PRA influences graft outcome also in transplants from HLA-identical siblings, indicating that non-HLA alloimmunity must play an important role in kidney transplantation (4). In the CTS Serum Study pretransplant presence of non-HLA MICA antibodies were associated with poor outcome (5). Currently we are investigating the role of donor-specific MICA antibodies in kidney transplantation.

See also: Study Design

References:

  1. Süsal C, Pelzl S, Opelz G. Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30. J Am Soc Nephrol 13: 1650-1656, 2002.
  2. Süsal C, Döhler B, Ruhenstroth A, Morath C, Slavcev A, Fehr T, Wagner E, Krüger B, Rees M, Balen S, Živcic-Cosic S, Norman DJ, Kuypers D, Emonds MP, Pisarski P, Bösmüller C, Weimer R, Mytilineos J, Scherer S, Tran TH, Gombos P, Schemmer P, Zeier M, Opelz G. A Collaborative Transplant Study Report. Donor-specific antibodies require preactivated immune system to harm renal transplant. EBioMedicine 9: 366-371, 2016.
  3. Schaefer SM, Süsal C, Opelz G, Döhler B, Becker LE, Klein K, Sickmüller S, Waldherr R, Macher-Goeppinger S, Schemmer P, Beimler J, Zeier M, Morath C. Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients. HLA 87: 89-99, 2016.
  4. Opelz G. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 365: 1570-1576, 2005.
  5. Zou Y, Stastny P, Süsal C, Döhler B, Opelz G. Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med 357: 1293-1300, 2007.


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