1  INTRODUCTION
Acquired aplastic anemia (AA) is characterized by pancytopenia caused by bone marrow failure without dysplasia or fibrosis. Both clinical and laboratory evidence support that pathogenesis of bone marrow failure is due to injury to hematopoietic stem cells (HSCs) by abnormal immunity1,2. Overall, research on depletion of HSCs in AA has focused on exploring the mechanism by which abnormal immunity attacks HSCs. However, no specific antibodies or immune cells targeting HSCs have been found to date. Therefore, the ”immune-mediated pathogenesis” of AA has not yet clarified how immune disorders specifically damage HSCs rather than other cells in bone marrow.
With in-depth study of bone marrow microenvironment, immune privileged (IP) sites of bone marrow specific to HSCs are discovered3. IP sites are mainly comprised of CD4+CD25+FoxP3+regulatory T cells (Tregs) which surround HSCs near the endosteal surface, providing an immune tolerance microenvironment for HSCs to protect HSCs from infection, radiation and other stress damage. This urged us to shift the research on depletion mechanism of HSCs in AA from immune “attack” to “protection loss” of IP. In fact, IP sites also exist in other tissues, and their abnormal pathogenicity has been a concern in various diseases4. For example, IP sites in hair follicle provide protection for epithelial hair follicle stem cells, and functional impairment leads to destruction of epithelial hair follicle stem cells, which is the main pathological mechanism of persistent alopecia in alopecia areata5. The local immune tolerance status of IP sites can be determined by detecting FoxP3+/CD4+ cells with an immunohistochemical method6. But the correlation between the collapse of self-tolerance of bone marrow IP sites and AA has not been reported. This study aimed to clinically verify that HSCs failure in AA is closely related to IP abnormalities through the detection of bone marrow IP sites in AA, MDS, and countrol group, providing clinical supportive evidence of worth further study for the IP pathogenesis in AA.