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Donor-specific antibodies in sensitized recipients may cause kidney transplant rejection. Here the authors show that complement component C3 inhibition prolongs graft survival by inhibiting T and B cell proliferation/activation and hence tissue injury, despite antibody levels remaining unaffected.

There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients is increased due to preformed DSA detected at time of transplant or the reactivation of HLA memory after transplantation, causing acute and chronic AMR. Alternatively, de novo DSA that develops post-transplant due to inadequate immunosuppression and again may lead to acute and chronic AMR or even allograft loss. Circulating antibody, the final product of the humoral immune response, has been the primary target of desensitization and AMR treatment. However, in many cases these protocols fail to achieve efficient removal of all DSA and long-term outcomes of patients with persistent DSA are far worse when compared to non-sensitized patients. We believe that targeting multiple components of humoral immunity will lead to improved outcomes for such patients. In this review, we will briefly discuss conventional desensitization methods targeting antibody or B cell removal and then present a mechanistically designed desensitization regimen targeting plasma cells and the humoral response.

OBJECTIVES/GOALS: We sought to examine: 1) variability in center acceptance patterns for heart allografts offered to the highest-priority candidates, 2) impact of this acceptance behavior on candidate survival, and 3) post-transplantation outcomes in candidates who accepted first rank offer vs. previously declined offer. METHODS/STUDY POPULATION: In this retrospective cohort study, the US national transplant registry was queried for all match runs of adult candidates listed for isolated heart transplantation between 2007-2017. We examined center acceptance rates for heart allografts offered to the highest-priority candidates and accounted for covariates in multivariable logistic regression. Competing risks analysis was performed to assess the relationship between center acceptance rate and waitlist mortality. Post-transplantation outcomes (patient survival and graft failure) between candidates who accepted their first-rank offers vs those who accepted previously declined offers were compared using Fine-Gray subdistribution hazards model. RESULTS/ANTICIPATED RESULTS: Among 19,703 unique organ offers, 6,302 (32%) were accepted for first-ranked candidates. After adjustment for donor, recipient, and geographic covariates, transplant centers varied markedly in acceptance rates (12%-62%) of offers made to first-ranked candidates. Lowest acceptance rate centers (

OBJECTIVES/GOALS: Lung transplant (LTx) candidates benefit from use of non-ideal donor organs. Each organ procurement organization (OPO) defines “acceptable” donor organs introducing unmeasured variation in donor pursuit. We characterized non-ideal donor pursuit among OPOs to identify drivers of risk aversion in LTx. METHODS/STUDY POPULATION: We queried the UNOS registry for adult donors who donated ≥1 organ for transplantation from 12/2007-12/2018. Non-ideal donors were those with any of age>50, smoking history ≥20 pack-years, PaO2/FiO2 (P/F) ratio

OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was