ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances - PubMed
5 hours ago
- #cell death
- #DADA2
- #metabolic disturbances
- ADA2-deficient cells show increased cell death and metabolic disturbances.
- DADA2 (Deficiency of adenosine deaminase 2) causes autoinflammation and immunodeficiency, often leading to bone marrow failure.
- ADA2-/- U-937 cells and PBMCs from DADA2 patients exhibit elevated cell death levels compared to wild-type ADA2 cells.
- Inhibitors of apoptosis, necroptosis, pyroptosis, and ferroptosis did not improve the viability of ADA2-deficient cells.
- Blocking TNF-alpha, type I interferon, and STING signaling, or reintroducing wild-type ADA2 protein, did not rescue cell death in vitro.
- ADA2-deficient cells display aberrant morphology, increased cell size and granularity, and impaired proliferative capacity.
- Metabolomics experiments revealed disturbances in the pentose phosphate pathway in ADA2-deficient cells.
- Increased intracellular reactive oxygen species exposure was observed in ADA2-deficient cells, attenuated post-hematopoietic stem cell transplantation in a DADA2 patient.
- The study suggests increased cell death and pentose phosphate pathway impairment as key pathomechanisms in DADA2.