Preliminary immunophenotyping in acquired Hemophilia A reveals an imbalanced immune activation landscape

Abstract

Abstract Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by the development of autoantibodies against the factor (F)VIII of coagulation. This can lead to severe spontaneous or post-traumatic bleeding, which is often potentially fatal. Although the pathophysiology of AHA has been partially elucidated, its comprehensive immunological profile remains unclear. Therefore, comprehending the immunophenotypic panorama and the interactions among these cells in patients is impending. Human peripheral blood mononuclear cells (PBMCs) were collected from both healthy donors (HDs) and AHA patients. Samples were analyzed using flow cytometry, and immunophenotypic characteristics were processed and visualized via FlowJo software. Due to the limited sample size, statistically significant differences were not observed yet. However, preliminary trends were evident. In AHA patients, T cell subsets showed distinct changes. Cytotoxic T cells and naïve T cells were decreased. In contrast, regulatory T cells (Tregs), Th1-like helper T cells (Th1 cells), memory T cells, activated/induced T cells (HLA-DR⁺), and senescent T cells (CD57⁺) were all increased. A trend toward a higher Th1/Th2 ratio was also noted. Additionally, mature neutrophils were elevated, while classical and intermediate monocytes, as well as myeloid-derived suppressor cells (MDSCs), were reduced. These findings suggest that AHA is associated with aberrant T cell activation, upregulation of pro-inflammatory neutrophils, and downregulation of multiple immune-regulatory cell populations. These findings indicate a possible link to immune imbalance and systemic inflammation. Further studies incorporating larger cohorts and single-cell sequencing are underway to better elucidate intercellular immune interactions in AHA.