Immunological Mechanisms of Haematopoietic Stem Cell Destruction in Severe Aplastic Anaemia: An Original T Regulatory Cell and Cytokine Profiling Study in Nigerians

This dissertation conducts an original investigation of T regulatory cell (Treg) biology and pro-inflammatory cytokine profiling in Nigerian patients with severe aplastic anaemia (SAA), developing a mechanistic immunological framework that explains the autoimmune destruction of haematopoietic stem cells in the Nigerian patient population. SAA is driven by autoreactive T cell-mediated HSC destruction, but the specific Treg deficiency profiles and cytokine signatures in African ancestry patients remain completely uncharacterised, limiting extrapolation from European and Asian immunosuppressive therapy data. A prospective case-control study enrolled 60 newly diagnosed SAA patients at Lagos University Teaching Hospital and Obafemi Awolowo University Teaching Hospital, 30 transfusion-dependent non-SAA aplastic controls, and 40 healthy controls. Peripheral blood Treg (CD4+CD25+FoxP3+) frequency and suppressive capacity were assessed by flow cytometry and co-culture suppression assays. Plasma cytokines (IFN-gamma, TNF-alpha, IL-17A, IL-2, TGF-beta, IL-35) were measured by multiplex immunoassay. T cell receptor Vbeta skewing was assessed by spectratyping. SAA patients showed a 61 percent reduction in Treg frequency and 73 percent reduction in Treg suppressive capacity compared to healthy controls. IFN-gamma and IL-17A were markedly elevated in SAA patients and negatively correlated with absolute neutrophil count. Treg suppressive capacity predicted immunosuppressive therapy response at six months with 78 percent accuracy. An original Nigerian SAA Immunopathology Framework incorporating Treg-cytokine axis data is proposed for guiding personalised immunosuppressive therapy selection. Keywords: aplastic anaemia, T regulatory cells, cytokines, immunopathology, Nigeria.