Genetic susceprtibity to acute or chronic schistosomiasis japonica

急、慢性日本血吸虫病的遗传易感性

• 批准号: 09470071
• 负责人: HIRAYAMA Kenji
• 金额: $ 8.32万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470071/
• 关键词: Schistosona japonicum; Major antigen; inmunogenetics; cDNA library; China; Protective immunity; vaccine; pig; 日本住血吸虫; 主要抗原; 免疫遺伝学; cDNAライブラリー; 中国; 感染防御; ワクチン; ブタ; 日本住吸血虫; 肝線維症; HLA; 超音波診断; ELISPOT法; 再感染抵抗性; 高リスク集団; サイトカイン; 集団治療

1.Molecular cloning of the major antigens from a cDNA library of schistosomal egg by using patients pooled sera.We have already found there are relatively resistant and susceptible HLA-class II haplotypes present in the Chinese patients against post-schistosomal liver fibrosis. This 'ear we seeked for the major antigens that would stimulate those HLA haplotypes positive individuals' T cells, because T cell response is assumed to be the most important in the pathogenesis. A cDNA library was prepared from a mRNA extracted from the freshly isolated eggs of a Chinese strain using lambda gt11 I phage system and was screened for the major antigens reactive with pooled sera by IgG detection system. Finally 200 positive clones were isolated and 146 clones out of those were directly sequenced. The result was unexpected because all the clones were several parts of one gene named miracidial antigen. The cloned gene was successfully expressed by GST fusion protein system.2. Re-infection study in t … More hree different villages.We have found two things. One is that there was no age dependent resistance in the population and the other is that there were two categories of people present, resistant and susceptible against re-infection. We have found that the HLA-DRB1 types that resistant persons had shared its 67th amino acid, phenylalanine, instead of having 67 leucine or isoleucine. Because the 67F or I/L is important to make a binding pocket, it would be critical to provoke some protective immune response.3. Vaccination trial of domestic pigs with recombinant paramyosin in China.In the endemic area in China, it is important to control the infection of the reservoir hosts, such as pigs and water buffaloes. We have performed a vaccine trial study using domestic pigs and recombinant paramyosin. The extensive study using more than 80 pigs revealed that the pigs were susceptible to challenge infection and were provoked immunity against infection after the vaccination with paramyosin as well as with attenuated cercariae (Vaccine in Press). Less

1.用患者血清从人肝细胞卵cDNA文库中克隆主要抗原，我们发现中国人肝细胞卵细胞后肝纤维化患者存在相对耐药和敏感的HLA-Ⅱ类单倍型。由于T细胞反应被认为在发病机制中是最重要的，因此我们寻找刺激HLA单倍型阳性个体T细胞的主要抗原。用λ gt 11 Ⅰ噬菌体系统从中国分离的一株鸡卵中提取mRNA，制备cDNA文库，用IgG检测系统筛选与混合血清反应的主要抗原。最后，分离到200个阳性克隆，其中146个克隆直接测序。结果出乎意料，因为所有克隆都是一个名为毛蚴抗原的基因的几个部分。利用GST融合蛋白系统成功表达了该基因. t中的再感染研究 ...更多信息 三个不同的村庄我们发现了两件事一个是在人群中没有年龄依赖性的抵抗力，另一个是存在两类人，抵抗和易受再感染。我们发现耐药者的HLA-DRB 1型共享其第67位氨基酸苯丙氨酸，而不是67位亮氨酸或异亮氨酸。由于67 F或I/L对于形成结合口袋很重要，因此激发一些保护性免疫应答至关重要。用重组副肌球蛋白免疫家猪的试验在我国流行区，控制猪和水牛等宿主的感染是非常重要的。我们使用家猪和重组副肌球蛋白进行了疫苗试验研究。使用超过80头猪进行的广泛研究表明，猪对攻毒感染易感，并在接种副肌球蛋白和减毒尾蚴后激发了抗感染免疫力（疫苗出版中）。少

项目成果

平山謙二: "寄生虫感染の重症化に関与する遺伝子"医学のあゆみ. 191(1). 124-130 (1999)

Kenji Hirayama：“与寄生虫感染严重程度相关的基因”，《医学史》191(1) (1999)。

太田伸生: "中国湖南省の日本住血吸虫病調査;揚子江流域の1村落をモデルとして" 熱帯. 30. 93-99 (1997)

Nobuo Ota：“中国湖南省日本血吸虫病调查；以长江流域的一个村庄为模型”热带。 30. 93-99 (1997)

平山謙二: "寄生虫感染の重症化に関する遺伝子"医学のあゆみ. 191(1). 124-130 (1999)

Kenji Hirayama：“与寄生虫感染严重程度相关的基因”，《医学史》191(1)。

Honggen Chen: "Vaccination of domestic pig with recombinant paramyosin against Schistosoma Japonicum in China"Vaccine. 2000.

陈宏根：“我国用重组副肌球蛋白接种家猪抗日本血吸虫”疫苗。

Kenji Hirayama et.al.: "HLA-DR-DQ alleles and HLA-DP alleles are independently associated with susceptibility to different stages of post-schistosomal hepatic fibrosis in the Chinese population." Tissue antigens.in press. (1999)

Kenji Hirayama 等人：“HLA-DR-DQ 等位基因和 HLA-DP 等位基因与中国人群对血吸虫后肝纤维化不同阶段的易感性独立相关。”