血小板缺乏性紫瘢症（ Idiopathic thrombocytopenia purpura， ITP）是一種常見的血小板疾病，病人體內之抗血小板自體抗體會破壞血小板而使血小板數目減少。尋找人體中自然存在之血小板自體抗原的 Epitopes 並了解自體抗體對血小板功能所產生的影響，為設計研發嶄新之 ITP 治療方式不可或缺的工作。我們希望研發 ITP 之專一性療法，解決現有療法之缺點。本計劃為全程執行期限 3 年之第 2 年計劃。我們在第 1 年計劃中以人類血小板注射小白鼠，利用活體內之自然免疫與抗原呈現作用製造單株抗體 (mAb)來篩選抗原性較強之血小板抗原。我們已經成功的篩選到一些可以分泌單株抗體的融合瘤細胞株。並成功地確認這些抗體的特性。此外，我們也發現上述單株抗體的確可以和臨床上 ITP 患者的血清互相競爭與血小板抗原結合。目前我們正在確認這些單株抗體的 Isotypes 與所認識的抗原種類。希望透過此方式在未來可以找尋自然存在於人體之血小板自體抗原，並於活體中分析其 mAb 對血小板破壞速率的影響。而最終之目的則是製造與血小板 Epitopes 結構相似之 Anti-idiotype antibody (AIAbs)，抑制 ITP 病人自體抗體與血小板結合，以研發 ITP 之專一性療法。 ITP is a common disorder that autoantibodies against platelets can result in platelets destruction and ultimately thrombocytopenia. Patients receiving current ITP interventions must confront to the disadvantages, such as side effects caused by non-specific intervention, expensive, and relapse. Accordingly, it should be a great interest to develop an ITP treatment that exhibits the advantages of specificity, convenience, cost-effectiveness and free of major side effects. In this project, we hope to develop a specific intervention for ITP to tackle the existed difficulties in clinical treatment. The present study is a 3-year study project. In the first year of project, we had successfully obtained several hybridomas that secreted high titer of anti-human platelet antibodies. Besides, these isolated monoclonal antibodies can compete the binding of platelet antigens with sera from ITP patients. The characteristics of these clones, isotypes of these monoclonal antibodies as well as the antigens recognized by these antibodies are now under investigating. Ultimate purposes of this 3-year study project are to identify new platelet autoantigen(s), study the kinetics of in vivo platelet destruction and develop an ITP-specific treatment taking the advantages of mAb and AIAb techniques.
