A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival

Abstract

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival Abstract Background Pretransplant donor-specific anti-HLA antibodies (DSA) are associated with impaired kidney graft survival, while the clinical relevance of non-donor specific anti-HLA antibodies (nDSA) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSA and nDSA. MethodsTo eliminate donor and era-dependent factors, a post-hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995-2005 with available pretransplant serum samples. Anti-HLA antibodies were detected with a luminex single antigen bead assay. ResultsAmong 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies.Patients with pretransplant DSA had a significantly lower 10-year death censored graft survival (55% vs. 82%, p=0.0001). Among 192 pairs with one recipient nDSA positive against either class I or II and the other without anti-HLA antibodies, graft survival did not significantly differ (74% vs. 77%, p=0.79).Only in patients with both nDSA class I and II there was a trend towards a lower graft survival (58%, p=0.06). Lastly, in a small group of 42 recipient pairs 10-year graft survival in recipients with DSA was 49% compared to 68% in recipients with nDSA (p=0.11). ConclusionThis paired kidney analysis confirms that the presence of pretransplant DSA in deceased donor transplantations is a risk marker for graft loss, whereas nDSA in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSA against class I and II, nDSA may be a risk marker for graft loss in the long term.

Specific amino acid patterns define split specificities of HLA-B15 antigens enabling conversion from DNA-based typing to serological equivalents

“…When an antibody against a B15 split antigen in the serum of the recipient is detected, the serological subtype of the B15 antigen present on the donor cells must be identified in order to determine whether this anti-B15 antibody is donor-specific. Because DSA can mediate and promote acute and chronic graft rejection, the presence of DSA is an important contraindication for solid organ transplantation (DeVos et al 2011 ; Michielsen et al 2019 ). In our current practice, high-resolution typing of HLA-B*15 is always performed for kidney patients and living donors.…”

Increased risk of rejection after basiliximab induction in sensitized kidney transplant recipients without pre‐existing donor‐specific antibodies – a retrospective study

“…In this setting, patients historically considered at low immunological risk should benefit from depleting induction therapy. On the other hand, the actual immunological risk in sensitized recipients (previously considered at high risk) is debated when no DSAs are identified before transplantation, since several recent reports have suggested that the risk of rejection may not be affected by nondonor‐specific anti‐HLA antibodies . With the increased risk of opportunistic infections and malignancies after rATG induction therapy, we have used basiliximab in sensitized patients without DSAs .…”

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

“…In a previous study of paediatric patients with sickle cell disease (SCD) undergoing chronic transfusion therapy with solely leukocyte‐reduced RBCs, one in three patients had HLA class I antibodies (Nickel et al , ). HLA alloimmunization has major implications in the transplant setting; patients with pre‐transplant donor‐specific HLA antibodies have decreased graft survival for both solid organ and HLA‐mismatched haematopoietic cell transplants (HCTs) (Ciurea et al , ; Spellman et al , ; Takanashi et al , ; Zachary & Leffell, ; Ciurea et al , ; Cutler et al , ; Ruggeri et al , ; Michielsen et al , ). In fact, current guidelines advise that patients being evaluated for HCT with HLA‐ mismatched donors should be screened for HLA antibodies to direct donor selection (Spellman et al , ; Yoshihara et al , ; Morin‐Zorman et al , ; Ciurea et al , ).…”