登革病毒，藉由病媒蚊的傳播，在熱帶及亞熱帶地區造成登革熱的流行。病毒感染引發的疾病包括登革熱(DF)及嚴重致死的登革出血熱/登革休克症候群(DHF/DSS)。血小板低下(thrombocytopenia)及血管壁通透性增加(plasma leakage)是DHF/DSS二大特徵。引起低血小板的原因可能是血小板前趨細胞megakaryocyte受到破壞、內皮細胞活化增加血小板貼附，或是血小板受到直接的破壞。登革病毒感染可能有分子模擬(molecular mimicry)機制的參與，已有報告指出病人血清中可以偵測到IgM抗血小板抗體的產生，且與病毒非結構性蛋白1(NS1)有交互作用，並能在補體作用下導致血小板裂解。單核球細胞是登革病毒主要感染標的細胞，感染後釋放大量細胞激素如IFN-γ。登革病症在許多病徵上與噬血性症候群(hemophagocytic syndrome)相似，病人骨髓抽出液可觀察到被組織球(histiocyte)吞噬的紅血球、白血球、血小板。我們也發現在急性期的病人血清可以偵測到代表單核球活化的鐵蛋白(ferritin)上升。因此我們推測登革病毒感染可能造成極度活化的單核球細胞，進而對宿主細胞進行破壞。我們的實驗發現，血小板在與病人血清培養後會釋放血清素(serotonin)而活化;IFN-γ活化的巨噬細胞對於血小板有比較強的吞噬能力，而且被病人血清或抗登革單株抗體調理過的血小板(opsonized platelet)經由抗體依靠性細胞吞噬作用(antibody-dependent cellular phagocytosis)，能夠大幅提高被巨噬細胞吞噬的機率。綜合以上結果，登革病毒感染造成的低血小板應該與免疫致病理論(immuno-pathogenesis)有一定的相關，即宿主體內活化的巨噬細胞，透過釋放細胞激素或者是直接的吞噬血小板導致血小板數目急劇降低，而抗血小板自體抗體則扮演促進吞噬的角色，使得血小板破壞更為嚴重。

Dengue virus is an arthropod borne virus transmitted by Ades egypti and Ades albopictus. The disease spectrum after dengue virus infection includes self-limited dengue fever (DF) and more seriously life-threatening dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS). Thrombocytopenia and plasma leakage are the two major characteristics of DHF/DSS. Several reasons are proposed for the cause of thrombocytopenia: megakaryocytes were suppressed in bone marrow, endothelium cells activation sequestered the adhesive platelets, and platelets were damaged and consumed directly. Molecular mimicry is reported to involve in dengue virus infection because anti-platelet IgM antibodies were detected and express cross-reactivity with viral NS1 proteins. Monocytes are the major target cells during dengue virus infection, and cytokines overproduction was shown. In DHF patients, it was found that red cells, white cells and platelets been phagocytozed by histiocytes in the bone marrow. These characteristics share similarities with hemophagocytic syndrome. In our studies, we found that serum ferritin level was elevated in dengue patients that correlated with the disease severity. Dengue patients contain IgM or IgG anti-platelet antibodies. Incubation of dengue patient’s sera with platelets will lead to platelets activation such as serotonin release; furthermore, the IFN-γ activated macrophages will phagocytoze more antibody-opsonized platelets. Therefore, we propose that thrombocytopenia is mediated by immune-mediated damage; the autoantibodies play a major role in this process.

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