Cheng Hsien-Jen, Luo Yueh-Hsia, Wan Shu-Wen, Lin Chiou-Feng, Wang Shan-Tair, Hung Nguyen Thanh, Liu Ching-Chuan, Ho Tzong-Shiann, Liu Hsiao-Sheng, Yeh Trai-Ming, Lin Yee-Shin
Institute of Basic Medical Sciences, Department of Microbiology and Immunology, Institute of Clinical Medicine, Institute of Gerontology, Department of Pediatrics, Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan; Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dengue Hemorrhagic Fever, Children's Hospital No. 1, Ho Chi Minh City, Vietnam.
Institute of Basic Medical Sciences, Department of Microbiology and Immunology, Institute of Clinical Medicine, Institute of Gerontology, Department of Pediatrics, Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan; Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dengue Hemorrhagic Fever, Children's Hospital No. 1, Ho Chi Minh City, Vietnam
Am J Trop Med Hyg. 2015 May;92(5):989-95. doi: 10.4269/ajtmh.14-0162. Epub 2015 Mar 9.
We have previously shown that anti-dengue virus nonstructural protein 1 (anti-DENV NS1) antibodies cross-react with endothelial cells, and several autoantigens have been identified. This study shows that the antibody levels against these self-proteins are higher in sera from patients with dengue hemorrhagic fever (DHF) than those in control sera. Anti-protein disulfide isomerase (PDI) and anti-heat shock protein 60 (anti-HSP60) IgM levels correlated with both anti-endothelial cells and anti-DENV NS1 IgM titers. A cross-reactive epitope on the NS1 amino acid residues 311-330 (P311-330) had been predicted. We further found that there were higher IgM and IgG levels against P311-330 in DHF patients' sera than those in the control sera. In addition, correlations were observed between anti-PDI with anti-P311-330 IgM and IgG levels, respectively. Therefore, our results indicate that DENV NS1 P311-330 is a major epitope for cross-reactive antibodies to PDI on the endothelial cell surface, which may play an important role in DENV infection-induced autoimmunity.
我们之前已经表明,抗登革病毒非结构蛋白1(抗DENV NS1)抗体与内皮细胞发生交叉反应,并且已经鉴定出几种自身抗原。本研究表明,登革出血热(DHF)患者血清中针对这些自身蛋白的抗体水平高于对照血清中的水平。抗蛋白二硫键异构酶(PDI)和抗热休克蛋白60(抗HSP60)IgM水平与抗内皮细胞和抗DENV NS1 IgM滴度均相关。已预测到NS1氨基酸残基311 - 330(P311 - 330)上存在一个交叉反应表位。我们进一步发现,DHF患者血清中针对P311 - 330的IgM和IgG水平高于对照血清中的水平。此外,分别观察到抗PDI与抗P311 - 330 IgM和IgG水平之间存在相关性。因此,我们的结果表明,DENV NS1 P311 - 330是内皮细胞表面与PDI发生交叉反应抗体识别的主要表位,这可能在DENV感染诱导的自身免疫中起重要作用。