Integrative omics and phase IIa clinical trial identify TNF as key node in autoimmune hepatitis - PubMed
5 hours ago
- #Autoimmune hepatitis
- #Infliximab
- #TNF
- Integrative omics and a phase IIa clinical trial identified TNF as a central node in autoimmune hepatitis (AIH).
- AIH patients face increased mortality and severe side effects from non-specific immunosuppressive therapy, necessitating targeted treatments.
- The study used computational modeling, multi-omics analyses, and functional experiments to map the immune landscape of AIH.
- A steroid-free, open-label phase IIa clinical trial tested infliximab, a TNF-targeting antibody, in AIH patients.
- Findings showed that myeloid cells and hepatocyte-derived IL-15 promote cytotoxicity and proliferation of auto-aggressive CD8+ T cells.
- TNF from clonally expanded liver-resident CD4+ T cells licenses the full cytotoxic program of these CD8+ T cells.
- AIH hepatocytes increase adhesion molecule expression in response to TNF, making them targets for both CD8+ and CD4+ T cells.
- Infliximab demonstrated efficacy as a steroid-free treatment in the clinical trial.
- The study identifies TNF as a central network node in AIH, paving the way for targeted, steroid-free therapies.
- The research advances understanding of AIH pathogenesis and supports broader application of immune-targeted therapies in autoimmune liver diseases.