Human Immunology Core

CONCLUSION: The Telenephrology Dashboard was developed using a Human-Centered Design approach to improve remote nephrology consultations. Future efforts will focus on evaluating its impact on user satisfaction, referring clinician satisfaction, access to nephrology care, and patient care outcomes.

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole...

Immune thrombotic thrombocytopenic purpura (iTTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular occlusion secondary to acquired ADAMTS13 deficiency. Contemporary data regarding iTTP treatment practices in the US, including the use of caplacizumab, are lacking. We aimed to characterize the demographics and therapies, including medications and apheresis practices, in patients with iTTP in the US. We retrospectively analyzed iTTP cases at 15 sites in the...

Production of antibodies against protein-based therapeutics (e.g., monoclonal antibodies (mAbs)) by a recipient's immune system can vary from benign symptoms to chronic neutralization of the compound, and in rare cases, a lethal cytokine storm. One critical factor that can induce or contribute to an anti-drug antibody (ADA) response is believed to be the presence of aggregated proteins in protein-based therapeutics. There is a high level of variability in the aggregation of different proteins,...

Early detection of viral infection and rapid activation of host antiviral defenses through transcriptional upregulation of interferons (IFNs) and IFN-stimulated genes (ISGs) are critical for controlling infection. However, aberrant production of IFN in the absence of viral infection leads to auto-inflammation and can be detrimental to the host. Here, we show that the DNA-binding transcriptional repressor complex composed of Capicua (CIC) and Ataxin-1 like (ATXN1L) binds to an 8-nucleotide motif...

Type 2 inflammatory diseases are common in cystic fibrosis (CF) including asthma, sinusitis, and allergic bronchopulmonary aspergillosis. CD4+ T helper 2 (Th2) cells promote these diseases through secretion of IL-4, IL-5, and IL-13. Whether the cystic fibrosis transmembrane conductance regulator (CFTR), the mutated protein in CF, has a direct effect on Th2 development is unknown. Using murine models of CFTR deficiency and human CD4+ T cells, we show CD4+ T cells expressed Cftr transcript and...

Beyond first line, the prognosis of relapsed/refractory (R/R) acute myeloid leukemia (AML) patients is poor with limited treatment options. Bemcentinib is an orally bioavailable, potent, highly selective inhibitor of AXL, a receptor tyrosine kinase associated with poor prognosis, chemotherapy resistance and decreased antitumor immune response. We report bemcentinib monotherapy and bemcentinib+low-dose cytarabine combination therapy arms from the completed BerGenBio-funded open-label Phase 1/2b...

Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines. This phase I, randomized, double-blind trial evaluated the safety...

CONCLUSIONS: One in 10 patients with childhood AIS had recent, asymptomatic VZV reactivation. In a vaccinated population, VZV may continue to play a modest role in childhood stroke pathogenesis.

Polychlorinated biphenyls (PCBs) remain an environmental health concern due to their persistence and ongoing release from legacy and emerging sources. 2,2',5,5'-Tetrachlorobiphenyl (PCB52), a PCB congener frequently detected in the environment and human blood, is oxidized to 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52). The neurotoxicity of this hydroxylated (OH-PCB) metabolite remains poorly characterized. In this study, we exposed 4-week-old male Sprague Dawley rats to 4-52 via a polymeric...