The results provide evidence that XTHs can act as cell wall-loosening enzymes.

In this cohort study (n = 935 transplantations), we investigated the phenotype and risk of graft failure in patients with histological criteria for antibody-mediated rejection (ABMR) in the absence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA), and compared this to patients with definite ABMR and HLA-DSA-positivity. The histological picture did not differ between HLA-DSA-positive (n = 85) and HLA-DSA-negative (n = 123) cases of ABMR histology, apart from increased complement split product 4d (C4d) deposition in the peritubular capillaries in HLA-DSA-positive cases. Histology of ABMR without HLA-DSA was more transient than DSA-positive ABMR, and patients with ABMR histology without HLA-DSA had graft survival superior to that of HLA-DSA-positive patients, independent of concomitant T cell-mediated rejection (38.2%) or borderline changes (17.9%). Multivariate analysis showed that the risk of graft failure was not higher in patients with histological picture of ABMR (ABMR ) in the absence of HLA-DSA, compared to patients without ABMR . Despite an association between C4d deposition and HLA-DSA-positivity, using C4d deposition as alternative for the DSA criterion in the diagnosis of ABMR, as proposed in Banff 2017, did not contribute to the prognosis of graft function and graft failure. We concluded that biopsies with ABMR but without detectable HLA-DSA represent a distinct, often transient phenotype with superior allograft survival.

BackgroundIn kidney transplantation, evaluating mismatches of HLA eplets—small patches of surface-exposed amino acids of the HLA molecule—instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes.MethodsTo evaluate the effect of number of eplet mismatches (mismatch load) on de novo formation of donor-specific HLA antibodies (DSAs) and transplant outcomes, we conducted a cohort study that included consecutive adult kidney recipients transplanted at a single center from March 2004 to February 2013. We performed retrospective high-resolution genotyping of HLA loci of 926 transplant pairs and used the HLAMatchmaker computer algorithm to count HLA eplet mismatches.ResultsDe novo DSAs occurred in 43 (4.6%) patients. Multivariable analysis showed a significant independent association between antibody-verified eplet mismatch load and de novo DSA occurrence and graft failure, mainly explained by DQ antibody-verified eplet effects. The association with DQ antibody-verified eplet mismatches was linear, without a safe threshold at which de novo DSA did not occur. Odds for T cell– or antibody-mediated rejection increased by 5% and 12%, respectively, per antibody-verified DQ eplet mismatch.ConclusionsEplet mismatches in HLA-DQ confer substantial risk for de novo DSA formation, graft rejection, and graft failure after kidney transplantation. Mismatches in other loci seem to have less effect. The results suggest that antibody-verified HLA-DQ eplet mismatch load could be used to guide personalized post-transplant immunosuppression. Adoption of molecular matching for DQA1 and DQB1 alleles could also help to minimize de novo DSA formation and potentially improve transplant outcomes.

In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the singleantigen beads assay but complement-dependent cytotoxicity crossmatch-negative.Donor specificity of the preDSA (N = 107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ. Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody-mediated rejection (ABMR h ; 54% and 59% respectively). Patients with preDSA that persisted posttransplant had worse 10-year graft survival compared to resolved DSA and preDSA-negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (hazard ratio [HR] = 8.3) but also in the absence (HR = 4.3) of ABMR h . In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMR h . Even in the absence of antibody-targeting therapy, low median fluorescence intensity DSA and non-DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome. K E Y W O R D S alloantibody, antibody-mediated (ABMR), clinical research/practice, deceased, donors and donation, health services and outcomes research, histocompatibility, kidney transplantation/ nephrology, major histocompatibility complex (MHC), organ procurement and allocation, rejection, risk assessment/risk stratification 1 | INTRODUC TI ON With the introduction of the complement-dependent lymphocytoxicity crossmatching (CDC-XM), donor-specific antibodies (DSA) have been established as the main determinant of successful | 3101 SENEV Et al.

Human leukocyte antigen (HLA) mismatches influence long-term graft outcome, 1 by the associated risk of T cell-mediated rejection. 2 Moreover, the presence of antibodies that react with the mismatched donor's HLA type cause antibody-mediated rejection (ABMR) and premature graft failure. 3-5 Therefore, in most transplant organizations, an HLA matching strategy was introduced. Organ allocation