“…Gritsch et al (8) reported an insignificant difference in graft survival with HLA-DR matching in 1585 pediatric recipients of a first deceased donor 35 years or younger, whereas contradictory findings are offered in other database analyses (9,10). A recent large single-center report of 178 recipients 21 years or younger describes a significant impact of HLA-DR matching on rejection rates, which was a strong predictor of graft loss and sensitization (11). Meier-Kriesche et al (12) described the association between HLA (A, B, DR) mismatching in the primary transplant and change in PRA level on relisting and noted a much stronger relationship of HLA mismatching and sensitization in the younger recipient.…”
In pediatric recipients, increasing number of initial HLA-DR MMs is associated with HLA sensitization, longer waiting time, decreased rate of retransplant, and decreased regraft survival. Consideration of DR matching at first transplant may mitigate these risks.
“…Gritsch et al (8) reported an insignificant difference in graft survival with HLA-DR matching in 1585 pediatric recipients of a first deceased donor 35 years or younger, whereas contradictory findings are offered in other database analyses (9,10). A recent large single-center report of 178 recipients 21 years or younger describes a significant impact of HLA-DR matching on rejection rates, which was a strong predictor of graft loss and sensitization (11). Meier-Kriesche et al (12) described the association between HLA (A, B, DR) mismatching in the primary transplant and change in PRA level on relisting and noted a much stronger relationship of HLA mismatching and sensitization in the younger recipient.…”
In pediatric recipients, increasing number of initial HLA-DR MMs is associated with HLA sensitization, longer waiting time, decreased rate of retransplant, and decreased regraft survival. Consideration of DR matching at first transplant may mitigate these risks.
“…Although sensitisation had a significant effect, the strongest association with poor transplant outcome was two DR mismatches at both transplants [ 40 ]. A further paediatric study has shown an increased risk of rejection rates, sensitisation and transplant outcome with DR mismatch [ 58 ] and the risk of sensitisation seems to be greater in younger patients [ 59 ]. Fig.…”
Section: Effects Of Preformed Hla Antibodiesmentioning
Human leukocyte antigen (HLA) sensitisation occurs after transfusion of blood products and transplantation. It can also happen spontaneously through cross-sensitisation from infection and pro-inflammatory events. Patients who are highly sensitised face longer waiting times on organ allocation programmes, more graft rejection and therefore more side effects of immunosuppression, and poorer graft outcomes. In this review, we discuss these issues, along with the limitations of modern HLA detection methods, and potential ways of decreasing HLA antibody development. We do not discuss the removal of antibodies after they have developed.
“…Human leukocyte antigen (HLA) matching significantly reduces the risk of graft rejection and graft failure after solid-organ transplantation [1–3] and graft-versus-host disease (GvHD) after hematopoietic stem-cell transplantation (HSCT) [4–9]. These pathological conditions evolve due to an alloreactive immune response that is initiated through interaction of allogeneic HLA with antibodies or the T-cell receptor (TCR).…”
Human leukocyte Antigen (HLA) mismatching leads to severe complications after solid-organ transplantation and hematopoietic stem-cell transplantation. The alloreactive responses underlying the posttransplantation complications include both direct recognition of allogeneic HLA by HLA-specific alloantibodies and T cells and indirect T-cell recognition. However, the immunogenicity of HLA mismatches is highly variable; some HLA mismatches lead to severe clinical B-cell- and T-cell-mediated alloreactivity, whereas others are well tolerated. Definition of the permissibility of HLA mismatches prior to transplantation allows selection of donor-recipient combinations that will have a reduced chance to develop deleterious host-versus-graft responses after solid-organ transplantation and graft-versus-host responses after hematopoietic stem-cell transplantation. Therefore, several methods have been developed to predict permissible HLA-mismatch combinations. In this review we aim to give a comprehensive overview about the current knowledge regarding HLA-directed alloreactivity and several developed in vitro and in silico tools that aim to predict direct and indirect alloreactivity.
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