Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4+ and CD8+ diabetogenic T cells. We have compared native epitopes versus mimotopes as well as various targeting signals in an effort to optimize recognition by both types of T cells in vitro. Optimal engagement of all T cells was achieved with segregation of CD8 and CD4 epitopes, the latter containing mimotopes and driven by endosome-targeting signals, after delivery into either dendritic or stromal cells. The CD4+ T cell responses elicited by the endogenously delivered epitopes were comparable with high concentrations of soluble peptide and included functional regulatory T cells. This work has important implications for the improvement of antigen-specific therapies using an epitope-based approach to restore tolerance in type 1 diabetes and in a variety of other diseases requiring concomitant targeting of CD4+ and CD8+ T cells.

BACKGROUND:The authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients with cancer. METHODS: The authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction-positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit. RESULTS: A total of 4184 hospitalized SARS CoV-2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [

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Severe factor XI (FXI) deficiency is a rare bleeding disorder with a prevalence of approximately one in 100 000 in the general population. 1 In certain populations such as Ashkenazi Jews, the prevalence is much higher with roughly 10% heterozygous for pathogenic variants with partial FXI deficiency phenotypes. 1 Increasingly, women without a bleeding history but with a mild FXI deficiency are identified by direct-to-consumer genetic testing. For instance, 23andMe recently received FDA authorization for diagnosis of the most common FXI mutations (ie F283L, E117X, and IVS14 + 1G>A). FXI levels do not reliably correlate with bleeding risk in pregnancy. 2-4 There are limited data to guide the appropriate management