Abstract
BackgroundIt 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. MethodsThe impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FindingsA 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. InterpretationPretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.
Highlights
More sensitive solid-phase assays based on ELISA, flow cytometry and Luminex® platforms were introduced for detection and specification of donor-specific HLA antibodies (DSA), and the pretransplant inclusion of HLA antibody specificities in the recipient's waiting list profile for allowing exclusion of ‘unacceptable HLA antigen mismatches' in the ‘virtual crossmatch’ has become routine practice (Tait et al, 2013)
Because of our previous failure to find an association of graft failure with pretransplant DSA that exclusively reacted in the exquisitely sensitive single antigen bead (SAB) assay (Susal et al, 2011), we focused in the present study on pretransplant sera containing complement-dependent cytotoxicity (CDC)- or ELISA-reactive antibodies, selected without regard to donor-specificity
All 385 presensitized patients as determined by CDC or ELISA testing were positive for HLA antibodies in the highly sensitive SAB assay, and 154 of the 385 (40%) possessed SAB-detected antibodies specific
Summary
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. 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. 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 b 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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