| Summary: | 博士 === 國立中興大學 === 轉譯醫學博士學位學程 === 105 === The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of antiphospholipid autoantibodies (APA), which targets β2-glycoprotein I (B2GPI)-anionic membrane phospholipids complex, and vascular thrombosis and/or pregnancy morbidities. As to its immunopathogenesis, we found no increase in plasma levels of high-mobility group box 1 (HMGB1), a danger-associated molecular pattern implicated in many autoimmune diseases, in APS patients. In a murine model of APS induced by active immunization of B2GPI, B2GPI-specific Th1, Th2 and Th17 responses were amplified in splenic T cells. Administration of DNA vaccine incorporating B2GPI, plus FK506, suppressed Th1 and Th17 response and upregulated Treg response in splenic T cells, in addition to the amelioration of the production of APA and APS manifestations. Therefore, it is speculated that the pathogenesis of APS, at least partly, originates from the imbalance between Th1, Th17 and Treg responses. Increased apoptosis can break the immune tolerance and contributes to the elicitation of aberrant autoimmune response. We revealed that plasma levels of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL), an apoptosis-inducing ligand, were in a trend to be elevated in APS patients when compared with healthy controls. Through these experiments, we aim to elucidate the immunological mechanism of APS and to provide new therapeutic opportunities in an immunological perspective.
|
|---|
