A study of the mechanism of bone marrow failure in hepatitis-associated aplastic anemia.

肝炎相关再生障碍性贫血骨髓衰竭机制的研究。

• 批准号: 13670792
• 负责人: KOJIMA Seiji
• 金额: $ 1.73万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670792/
• 关键词: Hepatitis; Aplastic Anemia; Apoptosis; Fas antigen; Hepatitis E; HLA; E型肝炎ウィルス; パルボB19ウィルス

Hepatitis-associated aplastic anemia (H-AA) is a varient of acquired AA, in which hepatitis precedes AA by a period of weeks to months. Both etiology of hepatitis and a mechanism of bone marrow failure are unknown. Although hepatitis E virus (HEV) was studied by HEVIgG and HEVIgM in 16 patients with H-AA, it was not detected in all of them. Based on our result, it is concluded that HEV is not a candidate virus for H-AA. We studied HLA antigen in 30pts. with H-AA, 60pts. with idiopathic AA and 250 normal controls. The frequencies of DR9 antigen was significantly increased in the pts. with H-AA, compared to pts, with idiopathic AA or normal controls (relative risk : 4.1). In pts with HAA, absolute numbers of total lymphocytes, especially CD4 lymphocytes are markedly decreased. We analyzed the expression of Fas antigen on peripheral lymphocytes and BM CD34+cells of pts. with AA. Higher expression of Fas antigen on peripheral lymphocytes and BM CD34+cells was found in pts. with H-AA than in pts. with idiopathic AA or normal controls. Expression of Fas-ligand was also increased on peripheral and BM CD+3 lymphocytes. These results suggest that increased programmed cell death though Fas/Fas ligand system in HLA restricted individuals is a possible mechanism of bone marrow failure in pts. with H-AA.

肝炎相关性再生障碍性贫血(H-AA)是获得性再生障碍性贫血的变种，肝炎先于再生障碍性贫血几周到几个月。肝炎的病因和骨髓衰竭的机制都是未知的。对16例H-AA患者进行了戊型肝炎病毒(HEV)检测，但均未检出HEV。根据我们的结果，HEV不是H-AA的候选病毒。我们对30例患者进行了人类白细胞抗原的检测。H-AA，60分。与特发性再生障碍性贫血和250名正常对照。PTS患者DR9抗原频率明显升高。与PTS、特发性再生障碍性贫血或正常对照组相比，H-AA患者的相对危险度为4.1。HAA患者外周血中总淋巴细胞绝对数明显减少，尤其是CD_4淋巴细胞。分析PTS患者外周血淋巴细胞和骨髓CD34+细胞表面Fas抗原的表达。和戒酒协会。PTS患者外周血淋巴细胞和BM CD34+细胞Fas抗原表达水平较高。用H-AA比在PTS中更好。患有特发性再生障碍性贫血或正常对照。外周血淋巴细胞和骨髓CD+3淋巴细胞Fas-Ligand表达增加。这些结果提示，人类白细胞抗原受限个体通过Fas/Fas配体系统增加程序性细胞死亡可能是PTS患者骨髓衰竭的一个可能机制。用H-AA。

项目成果

Ohara A, Kojima S, et al: "Evolution of myelodysplastic syndrome and acute myelogenous leukemia in children with hepatitis-associated aplastic anemia"Br J Haematol. 116. 999-1010 (2002)

Ohara A、Kojima S 等人：“肝炎相关再生障碍性贫血儿童中骨髓增生异常综合征和急性髓性白血病的演变”Br J Haematol。

Kojima S, et al: "Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiaion"Br J Haematol. 114. 706-711 (2001)

Kojima S 等人：“使用环磷酰胺、抗胸腺细胞球蛋白和全身照射对患有严重再生障碍性贫血的儿童进行无关供体骨髓移植”Br J Haematol。

Ihara M, Kojima S, et al.: "Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR ; comparison to detection of viral DNA in plasma by qualitative PCR"Microbiol Immunol.. 46. 701-705 (2002)

Ihara M、Kojima S 等人：“通过实时 PCR 监测骨髓移植受者的活动性 HHV-6 感染；与通过定性 PCR 检测血浆中的病毒 DNA 进行比较”Microbiol Immunol.. 46. 701-705（

Yoshimi A, Kojima S, et al: "Epstein-Barr virus specific T cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation"Br J Haematol. 116. 710-715 (2002)

Yoshimi A、Kojima S 等人：“在同种异体骨髓移植后患有淋巴细胞增殖性疾病的患者中，Epstein-Barr 病毒特异性 T 细胞毒性是通过穿孔素途径介导的”Br J Haematol。

Kojima S: "Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation"British Journal of Haematology. 114. 706-711 (2001)

Kojima S：“使用环磷酰胺、抗胸腺细胞球蛋白和全身照射对患有严重再生障碍性贫血的儿童进行无关供体骨髓移植”英国血液学杂志。