41 research outputs found
Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation
Non peer reviewe
Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation
PIRCHE-II Is Related to Graft Failure after Kidney Transplantation
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donorârecipient couples that were transplanted between 1995 and 2005. For these donorsârecipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04â1.23, pâ=â0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10â1.34, pâ<â0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival
Eigenvalue asymptotics for weighted Laplace equations on rough Riemannian manifolds with boundary
Our topological setting is a smooth compact manifold of dimension two or
higher with smooth boundary. Although this underlying topological structure is
smooth, the Riemannian metric tensor is only assumed to be bounded and
measurable. This is known as a rough Riemannian manifold. For a large class of
boundary conditions we demonstrate a Weyl law for the asymptotics of the
eigenvalues of the Laplacian associated to a rough metric. Moreover, we obtain
eigenvalue asymptotics for weighted Laplace equations associated to a rough
metric. Of particular novelty is that the weight function is not assumed to be
of fixed sign, and thus the eigenvalues may be both positive and negative. Key
ingredients in the proofs were demonstrated by Birman and Solomjak nearly fifty
years ago in their seminal work on eigenvalue asymptotics. In addition to
determining the eigenvalue asymptotics in the rough Riemannian manifold setting
for weighted Laplace equations, we also wish to promote their achievements
which may have further applications to modern problems
T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation
Antibodies against ARHGDIB are associated with long-term kidney graft loss
The clinical significance of nonâHLA antibodies on renal allograft survival is a matter of
debate, due to differences in reported results and lack of largeâscale studies incorporating analysis of multiple nonâHLA antibodies simultaneously. We developed a multiplex nonâHLA antibody assay against 14 proteins highly expressed in the kidney. In
this study, the presence of pretransplant nonâHLA antibodies was corre