Multi-Omics Profiling Identifies Pathways Associated With CD8⁺ T-Cell Activation in Severe Aplastic Anemia

Area of Science:

• Immunology
• Hematology
• Metabolomics

Background:

• Severe aplastic anemia (SAA) is an autoimmune disorder targeting hematopoietic stem cells.
• Autoreactive CD8+ T cells are implicated, but their activation mechanisms in SAA are unclear.

Purpose of the Study:

• To investigate the molecular mechanisms regulating pathogenic CD8+ T cell activation in severe aplastic anemia.
• To identify novel therapeutic targets for SAA treatment.

Main Methods:

• Proteomics and metabolomics analyses of plasma and bone marrow supernatant.
• Transcriptional analysis of CD8+ T cells from SAA patients and healthy donors.
• Analysis of single-cell RNA sequencing data and murine SAA models.

Main Results:

• Identified differential proteins and metabolites linked to energy metabolism, complement, coagulation, and HIF-1α signaling.
• Found enrichment of these pathways in SAA patient T cells.
• Discovered an increased CD38+ CD8+ T cell subset in SAA, associated with glycolysis and complement pathways.

Conclusions:

• SAA pathogenesis involves dysregulated energy metabolism and complement pathways in CD8+ T cells.
• The identified pathways and CD38+ subset represent potential therapeutic targets for SAA.