90%以上的成年人都曾經被EB病毒感染過，發病多以慢性潛伏性感染為主，但是在少數的病例中會因為急性感染而造成傳染性單核球增多症，進而併發噬血症候群(hemophagocytic syndrome, HS)。噬血症候群起因於病人體內免疫系統對病毒感染的過度活化，釋出細胞激素(cytokines)，導致吞噬細胞活化。但吞噬細胞活化後如何吞噬血球，則一直是一個謎。吞噬細胞的吞噬作用必須經由表面上的受體來辨識外來的分子(ligand)，其中一個可能的途徑是經由Fc受體。EB病毒感染後，是否會促使B細胞產生對抗血球的抗體進一步來引起吞噬作用，是本研究的主要目的。
　　在本研究中，我們進行三個實驗來澄清上述的假說。我們首先觀察活化的吞噬細胞株U937細胞對紅血球的吞噬作用。活化的U937細胞會吞噬被抗體標定的紅血球，而對於沒有抗體標定的紅血球則沒有任何吞噬現象。其次，我們利用臨床噬血症侯群病人血清檢體來檢查是否有對抗紅血球的抗體存在。我們經由疾病管制局收集了68個噬血症候群病人的血清，有18個血清抗紅血球抗體呈陽性反應。其中36個病人與EB病毒感染有關，11個呈抗體陽性反應。上述的體外及人體實驗中，皆顯示吞噬細胞的吞噬作用確與對紅血球的自體抗體的產生有關。接下來我們利用一個已建立的一個EB病毒感染誘發噬血症候群的動物模式來進一步證實這個假說。我們以Herpesvirus papio(HVP)感染紐西蘭白兔，在九隻HVP感染的兔子中，我們發現病毒感染13天後，紅血球表面開始出現抗體(1.8%)，一直到感染後26天(92.8%)皆可測到抗紅血球抗體的存在；同時伴隨著抗體的出現，在淋巴結的切片中觀察到血球吞噬的現象。
　　因此，由上述三項實驗，我們認為當EB病毒急性感染時，會使T細胞過度活化，並激活吞噬細胞。同時，B細胞會產生抗紅血球抗體，並進一步造成噬血症候群。藉由此實驗，我們對於噬血症候群的血球吞噬現象提出了一個可能的機轉。

　　The pathogenic basis of hemophagocytic syndrome (HS) is the over activation of the immune system, in particular the lymphocytes and macrophage. Among the infection-associated HS, Epstein-Barr virus (EBV) infection is the causative agent in most cases. In EBV-associated HS, unregulated T-cell reaction may release high levels of cytokines�n which lead to activation of macrophage and induced hemophagocytic syndrome. However, the mechanism of hemophagocytosis in HS remains unknown. Since phagocytosis by macrophages depends on a receptor mediated mechanism, we hypothesize that the hemophagocytosis might occur through the Fc-Fc receptor pathway. The specific aim of this study is to identify the existence of anti-RBC Ab in EBV-associated HS.
　　In this experiment, we first studied whether the phagocytosis of red cells by activated U937 cell is antibody-dependent. We demonstrated that the phagocytosis by macrophage could be observed only in the presence of Ab-conjugated RBC and not in normal RBC. Second, we collected 68 serum samples of patients with HS from Taiwan CDC and detected the existence of autoantibodies to red cells. After Ab screening, serum samples from 18 of 68 HS patients were anti-RBC Ab positive. among them, 36 samples were EBV positive and 11()had detected autoantibodies to red cells. These two studies suggest that anti-RBC Ab may play a role in the development of HS. In order to further test the hypothesis, we established an EBV-infection animal model. We infected 9 rabbits with Herpesvirus papio(HVP) , and found that anti-RBC Ab was detectable on the surface of RBCs (1.8%) after 13 days infection of virus , and increased up to 92.8% on 26th day. Also, hemophagocytosis in lymph node can be observed after the appearance of anti-RBC Ab.
　　Our experiments demonstrate that acute infection of EBV would not only lead to the activation of T cell and macrophage, but also activate the B cell to induce the production of anti-RBC Ab. The presence of autoantibodies to red cells is essential for hemophagocytosis in EBV-associated HS. Our studies provide a potential mechanism of hemophagocytosis in EBV-associated HS.

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