Latent EBV impairs immune cell signaling and enhances the efficacy of anti-CD3 mAb in Type 1 Diabetes.
Ana Lledo DelgadoPaula Preston-HurlburtNoha LimTomokazu S SumidaS Alice LongJames McNamaraElisavet SertiLauren HigdonKevan C HeroldPublished in: medRxiv : the preprint server for health sciences (2023)
Teplizumab has been approved for the delay of the onset of type 1 diabetes and may modulate new onset disease. We found that patients who were EBV positive at baseline had a more robust response to drug in two clinical trials and therefore postulated that latent virus has general effects in modifying immune responses. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and partially exhausted CD8 + T cells were found in EBV seropositive individuals at the baseline in the TN10 trial and AbATE trial. Single cell transcriptomics and functional assays identified downregulation of the T cell receptor and other signaling pathways before treatment. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways generally in immune cells, that broadly redirect cell differentiation.
Keyphrases
- epstein barr virus
- clinical trial
- single cell
- type diabetes
- diffuse large b cell lymphoma
- signaling pathway
- peripheral blood
- study protocol
- cardiovascular disease
- randomized controlled trial
- emergency department
- rna seq
- metabolic syndrome
- cell proliferation
- machine learning
- combination therapy
- pi k akt
- artificial intelligence
- cell cycle arrest
- drug induced