Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Abstract

The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

“…A detailed description of the cohort has been published previously. 10 Clinical data were obtained from the Dutch Organ Transplant Registry. Rejection was defined as the presence of biopsy-proved acute rejection (without further classification) or any treatment for acute rejection when no biopsy was performed.…”

Technical challenges and clinical relevance of single antigen bead C1q/C3d testing and IgG subclass analysis of human leukocyte antigen antibodies

“…Many studies using SAB technology revealed pre‐existence or de novo DSA particularly directed at HLA class II to be much more prevalent than was previously found by using less sensitive methods such as CDC or enzyme‐linked immunosorbent assay (ELISA) . Nevertheless, not all patients with DSA as defined by these highly sensitive SAB assays experience ABMR or poor graft survival , questioning the clinical relevance of HLA antibodies only detected in SAB assays. This differential pathogenicity of HLA antibodies could be attributed to differences in IgG subclass composition and complement‐fixing capacity, not detected in standard SAB assays.…”

“…In this regard, a positive CDC crossmatch (CDC‐XM) is considered a contraindication for transplantation. While higher sensitivity of flow cytometry crossmatch (FC‐XM) test enables detection of low titer HLA antibodies of all IgG subclasses, DSA detected by solid phase assays alone or in the presence of a positive FC‐XM result were shown to increase the risk of ABMR and graft failure albeit not accounting for high risk in every individual patient . Therefore, the presence of DSA which are not considered a contraindication for transplantation can be used for risk stratification and adaptation of immunosuppressive protocols.…”

“…Pre‐existence or de novo development of donor‐specific antibodies (DSA) directed to mismatched human leukocyte antigen (HLA) is known to be an important risk factor for developing antibody‐mediated rejection (ABMR), and a major cause of inferior graft survival . While currently available immunosuppressive agents are effective in controlling T cell‐mediated rejection and improving short‐term graft survival, they are inadequate in preventing or reversing ABMR, making this the leading cause of late graft loss .…”

Antibodies against ARHGDIB are associated with long-term kidney graft loss

“…Because our cohort contained a relatively high proportion of living donors and we previously found that DSA had mainly an impact on deceased-donor transplantations with only a limited effect on living-donor transplantations, 19 we also analyzed the impact of non-HLA antibodies on long-term graft survival according to donor status (3276 deceased-donor and 1494 living-donor transplantations). After deceased-donor transplantation, the AKME according to the presence of ARHGDIB antibodies showed a 10-year death-censored graft survival of 61% (95% CI 50%-70%) for the 94 of 3276 patients with and 73% (95% CI 71%-75%) for the 3182/3276 patients without ARHGDIB antibodies ( Table 2).…”