Acquired aplastic anemia (AA), the prototypical bone marrow (BM) failure syndrome, is caused by immune-mediated destruction of hematopoietic stem/progenitor cells (HSPCs). An immune mechanism was inferred decades ago from the recovery of hematopoiesis in patients who failed to engraft after stem cell transplantation, when renewal of autologous blood-cell production was credited to the conditioning regimen. The responsiveness of AA to immunosuppressive therapy (IST) in most patients is the best evidence of an underlying immune pathophysiology: the majority of patients show hematologic improvement after transient T-cell depletion by ATGs. The key goal of this project is to identify autoantigens presented by HLA molecules in AA patients using induced pluripotent stem cells (iPSCs) technology. The identification of autoantigens in AA could lead to the development of novel therapies that suppress immune responses specific to these autoantigens, as opposed to non-specific immunosuppressive therapies like ATG and cyclosporine. Moreover, this research has the potential to make significant contributions to the broader fields of medicine and immunology.
- Aplastic Anemia