HLA sensitization and allograft bone graft incorporation.
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ABSTRACT: UNLABELLED: Achieving union between host bone and massive structural allografts can be difficult. Donor and recipient human leukocyte antigen (HLA) mismatches and recipient antibody response to donor HLA antigens might affect union. In a prospective multiinstitutional study, we enrolled a consecutive series of patients receiving cortex-replacing, massive structural bone allografts to determine the rate of donor-specific HLA antibody sensitization and to investigate the potential effect of such HLA alloantibody sensitization on allograft incorporation. HLA typing of patients and donors was determined by molecular typing methods. Donor-specific HLA sensitization occurred in 57% of the patients but had no demonstrable effect on graft incorporation or union. The type of host-allograft junction did have a major effect on graft incorporation. Cortical-to-cortical allograft-to-host junctions healed more slowly (mean, 542 days) than corticocancellous to corticocancellous allograft-to-host junctions (mean, 243 days). Although HLA sensitization does not appear to delay structural allograft bone incorporation, further followup is required to determine if there is an association between HLA sensitization and long-term graft survival. Based on these preliminary data, measures to further minimize or modulate HLA sensitization or response are not indicated at present for the purposes of improving structural bone allograft union. LEVEL OF EVIDENCE: Level II, prognostic study.
Project description:Immune profiles were performed retrospectively in highly sensitized kidney transplant candidates Our hypothesis was that baseline differences in immune profiles could help identify candidates that respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in 20 highly sensitized kidney transplant candidates undergoing desensitization therapy.
Project description:Immune profiles were performed retrospectively in highly sensitized kidney transplant candidates Our hypothesis was that baseline differences in immune profiles could help identify candidates that respond to desensitization therapy.
Project description:The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(-) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(-) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499-15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT.
Project description:ObjectiveCompared to autologous bone grafts, allogeneic bone grafts integrate slowly, which can adversely affect clinical outcomes. Here, our goal was to understand the molecular mechanisms underlying graft incorporation, and then test clinically feasible methods to accelerate this process.MethodsWild-type and transgenic Wnt "reporter" mice were used in a vertical ridge augmentation procedure. The surgery consisted of tunneling procedure to elevate the maxillary edentulous ridge periosteum, followed by the insertion of bone graft. Micro-computed tomographic imaging, and molecular/cellular analyses were used to follow the bone graft over time. Sclerostin null mice, and mice carrying an activated form of β-catenin were evaluated to understand how elevated Wnt signaling impacted edentulous ridge height and based on these data, a biomimetic strategy was employed to combine bone graft particles with a formulation of recombinant WNT protein. Thereafter, the rate of graft incorporation was evaluated.ResultsTunneling activated osteoprogenitor cell proliferation from the periosteum. If graft particles were present, then osteoprogenitor cells attached to the matrix and gave rise to new bone that augmented edentulous ridge height. Graft particles alone did not stimulate osteoprogenitor cell proliferation. Based on the thicker edentulous ridges in mice with amplified Wnt signaling, a strategy was undertaken to load bone graft particles with WNT; this combination was sufficient to accelerate the initial step of graft incorporation.SignificanceLocal delivery of a WNT protein therapeutic has the potential to accelerate graft incorporation, and thus shorten the time to when the graft can support a dental implant.
Project description:Recurrent instability after anterior shoulder stabilization surgery is not an uncommon complication, with variable rates of recurrences associated with different surgical procedures. The Latarjet procedure continues to be the gold standard in the management of anterior instability with significant glenoid bone loss, although a recent trend toward arthroscopic anatomic glenoid reconstruction (AAGR) with distal tibial allograft has been noted, with excellent short-term results and minimal complication rates. Arthroscopic revision stabilization for failed stabilization procedures is increasingly being performed, although it is technically more challenging than the primary stabilization procedure because of the anatomic rearrangements of the index surgery. In this article, we describe a revision arthroscopic technique for anatomic glenoid reconstruction using iliac crest autograft for a previous failed AAGR procedure secondary to nonunion of the graft. The graft is passed through the Halifax far-medial portal without splitting the subscapularis. Arthroscopic revision in the setting of a failed AAGR procedure is technically easier than after a Latarjet procedure, as the anatomy is relatively undisturbed in the former, facilitating easier identification of anatomic landmarks, accurate graft positioning, and decreased risk of neurovascular injuries. A Bankart capsulolabral repair is performed after graft fixation, making the graft extra-articular and providing additional stability.
Project description:BackgroundThe association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid (AA) mismatches (MMs) at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those MMs assessed at the antigenic (2-digit) specificity.MethodsData on 240 024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients. We imputed HLA-A, -B, and -DRB1 alleles and corresponding AA polymorphisms from antigenic specificity through the application of statistical and population genetics inferences. GF risk was evaluated using Cox proportional-hazards regression models adjusted for covariates including patient and donor risk factors and HLA antigen MMs.ResultsWe show that estimated AA MMs at particular positions in the peptide-binding pockets of HLA-DRB1 molecule account for a significant incremental risk that was independent of the well-known association of HLA antigen MMs with graft survival. A statistically significant linear relationship between the estimated number of AA MMs and risk of GF was observed for HLA-DRB1 in deceased donor and living donor transplants. This relationship was strongest during the first 12 months after transplantation (hazard ratio, 1.30 per 15 DRB1 AA MM; P < 0.0001).ConclusionsThis study shows that independent of the well-known association of HLA antigen (2-digit specificity) MMs with kidney graft survival, estimated AA MMs at peptide-binding sites of the HLA-DRB1 molecule account for an important incremental risk of GF.
Project description:Using light irradiation as a trigger, large-scale structural reconfiguration of DNA nanostructures is demonstrated. We incorporated photo-cleavable spacers at strategic locations within the short oligonucleotide strands connecting adjacent helices within a DNA origami sphere, and then used light to transform the sphere into two tethered hemispheres.
Project description:By taking advantage of the outstanding intrinsic optoelectronic properties of perovskite-based photovoltaic materials, together with the strong near-infrared (NIR) absorption and electronic confinement in PbS quantum dots (QDs), sub-bandgap photocurrent generation is possible, opening the way for solar cell efficiencies surpassing the classical limits. The present study shows an effective methodology for the inclusion of high densities of colloidal PbS QDs in a MAPbI3 (methylammonium lead iodide) perovskite matrix as a means to enhance the spectral window of photon absorption of the perovskite host film and allow photocurrent production below its bandgap. The QDs were introduced in the perovskite matrix in different sizes and concentrations to study the formation of quantum-confined levels within the host bandgap and the potential formation of a delocalized intermediate mini-band (IB). Pronounced sub-bandgap (in NIR) absorption was optically confirmed with the introduction of QDs in the perovskite. The consequent photocurrent generation was demonstrated via photoconductivity measurements, which indicated IB establishment in the films. Despite verifying the reduced crystallinity of the MAPbI3 matrix with a higher concentration and size of the embedded QDs, the nanostructured films showed pronounced enhancement (above 10-fold) in NIR absorption and consequent photocurrent generation at photon energies below the perovskite bandgap.
Project description:Synthetic materials based on calcium phosphate (CaP) are frequently used as bone graft substitutes when natural bone grafts are not available or not suitable. Chemical similarity to bone guarantees the biocompatibility of synthetic CaP materials, whereas macroporosity enables their integration into the natural bone tissue. To restore optimum mechanical performance after the grafting procedure, gradual resorption of CaP implants and simultaneous replacement by natural bone is desirable. Mg and Sr ions released from implants support osteointegration by stimulating bone formation. Furthermore, Sr ions counteract osteoporotic bone loss and reduce the probability of related fractures. The present study aimed at developing porous Ca carbonate biominerals into novel CaP-based, bioactive bone implant materials. Macroporous Ca carbonate biominerals, specifically skeletons of corals (aragonite) and sea urchins (Mg-substituted calcite), were hydrothermally converted into pseudomorphic CaP materials with their natural porosity preserved. Sr ions were introduced to the mineral replacement reactions by temporarily stabilizing them in the hydrothermal phosphate solutions as Sr-EDTA complexes. In this reaction system, Na, Mg, and Sr ions favored the formation of correspondingly substituted β-tricalcium phosphate over hydroxyapatite. Upon dissolution, the incorporated functional ions became released, endowing these CaP materials with bioactive and potentially osteoporotic properties.