Neutrophil-enriched gene signature correlates with teplizumab therapy resistance in different stages of type 1 diabetes.

ABSTRACT: Teplizumab, a humanized anti-CD3 mAb, represents a breakthrough in autoimmune type 1 diabetes (T1D) treatment, by delaying clinical onset in stage 2 and slowing progression in early stage 3 of the disease. However, therapeutic responses are heterogeneous. To better understand this variability, we applied single-cell transcriptomics to paired peripheral blood and pancreas samples from anti-mouse CD3-treated nonobese diabetic (NOD) mice and identified distinct gene signatures associated with the therapy outcome, with consistent patterns across compartments. Success-associated signatures were enriched in NK or CD8+ T cells and other immune cell types, whereas resistance signatures were predominantly expressed by neutrophils. The immune cell communities underlying these response signatures wer

SUBMITTER: Sassi G 

PROVIDER: S-EPMC12646666 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature