Study on Etiology and Pathogenesis of Kawasaki Disease

川崎病病因及发病机制研究

• 批准号: 07307011
• 负责人: KATO Hirohisa
• 金额: $ 12.22万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07307011/
• 关键词: Kawasaki disease; super antigen; T cell receptor; TNF-alpha; Vβレパトア; アポトーシス; Heat shock protein; HHV-6; HLA

To investigate genetic susceptibility to Kawasaki disease (KD), peripheral blood lymphocytes (PBL) were tested for TNF-a production in the presence of PHA and PMA.PBL from patients with convalescent KD and the compatriots produced higher amount of TNF-alpha than those from controls without KD.And HLA DNA typing revealed that DPB1^<**>0202 and DPB1^<**>0601 may relate to KD.These results suggested that KD may be controlled under the genetic factors.Mycobacterium 65 kDa heat shock protein gene were amplified using polymerase chain reaction (PCR) technique in 30% of blood samples from patients and Streptococcus haemolyticus were isolated from a few percents of patients with acute KD and anti-Yersinia pseudotuberculosis-antibody raised in 10% of convalescent patients. Furthermore studies are needed to clarify the relation of KD to those microorganisms.Parvovirus B19 gene was not detected using PCR technique in acute phase and anti-parvovirus B19 antibody did not rise in convalescent phase. … More We failed to fined any evidence that KD is caused by parvovirus B19.In study on pathogenesis of KD,superantigen hypothesis is important issue. Using T cell proliferation assay, supernatants positive were isolated from all 31 KD patients. Known superantigens could be detected in 16 patients. In the remaining supernatants, we are going to purify the protein which have proliferative activity. A fraction containing proliferative activity stimulated T cells bearing the specific T cell receptor but we were not able to relate KD to selective expansion of specific T cell receptor expressing T cells in freshly isolated peripheral blood lymphocytes. We observed apoptosis of lymphocytes in lymph node from acule KD patients but observation of T cells in peripheral blood did not indicate the possibility that T cells may be stimulated with superantigen. And with electron microscope activated macrophages were found in peripheral blood. The investigation of the possibility that superantigen may be the causative agents must be the subject of future research. Less

探讨川崎病（KD）的遗传易感性，用PHA和PMA对正常人外周血淋巴细胞（PBL）进行了TNF-α的检测，发现KD恢复期患者和正常人外周血淋巴细胞TNF-α的产生量均高于正常对照组，HLA-DNA分型结果显示DPB 1 ^**>0202和DPB 1 ^**> 0202与正常对照组比较差异有显著性（P <0.05）。用聚合酶链反应（PCR）技术扩增了30%的结核分枝杆菌65 kDa热休克蛋白基因（HSP 65 kDa），并对65 kDa HSP 65 kDa热休克蛋白基因的表达进行了分析结果：10%的患儿血标本分离到溶血性链球菌，少数患儿血清中抗假结核耶尔森菌抗体阳性率为10%，康复期的病人。PCR技术在急性期未检测到细小病毒B19基因，恢复期抗细小病毒B19抗体未升高。 ...更多信息 目前还没有发现任何证据表明KD是由细小病毒B19引起的。在KD发病机制的研究中，超抗原假说是一个重要的问题。采用T细胞增殖试验，对31例KD患儿的培养上清进行了检测。在16例患者中可以检测到已知的超抗原。在剩余的上清液中，我们将纯化具有增殖活性的蛋白。含有增殖活性的部分刺激具有特异性T细胞受体的T细胞，但我们不能将KD与新鲜分离的外周血淋巴细胞中表达特异性T细胞受体的T细胞的选择性扩增联系起来。我们观察到急性KD患者淋巴结中淋巴细胞凋亡，但外周血中T细胞的观察并不表明T细胞可能被超抗原刺激。电镜下可见外周血中有活化的巨噬细胞。超抗原可能是病原体的可能性的调查必须是未来研究的主题。少

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