Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity.
Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity.
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DOI：
10.1111/j.1365-2249.2005.02864.x
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发表时间：
2005-09
影响因子：
4.6
通讯作者：
Lei HY
中科院分区：
文献类型：
--
作者：
Lin YS;Lin CF;Fang YT;Kuo YM;Liao PC;Yeh TM;Hwa KY;Shieh CC;Yen JH;Wang HJ;Su IJ;Lei HY
严重急性呼吸综合征相关冠状病毒（SARS-CoV）感染的发病机制涉及病毒作用和免疫介导机制。在这项研究中，我们发现在SARS患者的血清中存在与A549细胞（2型肺细胞）反应的自身抗体（autoAbs），这些自身抗体主要是IgG。发热后20天检测到自身抗体。非SARS肺炎患者的检测未显示出与SARS患者相同的自身抗体产生。血清IgG与A549细胞结合后，诱导细胞毒性。细胞毒性与抗上皮细胞IgG水平呈正相关。预吸收和结合实验表明，在SARS-CoV刺突蛋白结构域2 （S2）上存在交叉反应性表位。此外，用抗s2抗体和IFN-γ处理A549细胞导致人外周血单个核细胞对这些上皮细胞的粘附性增加。综上所述，我们已经证明SARS患者血清中的抗s2抗体可引起细胞毒性损伤，并增强免疫细胞对上皮细胞的粘附。SARS- cov感染中自身免疫反应的发生可能与SARS发病机制有关。
Both viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-γ resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.