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

作者：Suesal Caner; Doehler Bernd; Ruhenstroth Andrea; Morath Christian; Slavcev Antonij; Fehr Thomas; Wagner Eric; Krueger Bernd; Rees Margaret; Balen Sanja; Zivcic Cosic Stela; Norman Douglas J; Kuypers Dirk; Emonds Marie Paule; Pisarski Przemyslaw; Boesmueller Claudia; Weimer Rolf; Mytilineos Joannis; Scherer Sabine; Tran Thuong H; Gombos Petra; Schemmer Peter; Zeier Martin; Opelz Gerhard

来源：EBioMedicine, 2016, 9: 366-371.

DOI：10.1016/j.ebiom.2016.06.006

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

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.

• 出版日期2016-7