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原发性胆汁性肝硬化及其他特发性胆汁疾病中逆转录病毒抗体的检测

Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders.

作者信息

Mason A L, Xu L, Guo L, Munoz S, Jaspan J B, Bryer-Ash M, Cao Y, Sander D M, Shoenfeld Y, Ahmed A, Van de Water J, Gershwin M E, Garry R F

机构信息

Section of Gastroenterology and Hepatology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.

出版信息

Lancet. 1998 May 30;351(9116):1620-4. doi: 10.1016/S0140-6736(97)10290-2.

Abstract

BACKGROUND

Retroviruses have been implicated in the aetiology of various autoimmune diseases. We used immunoblots as a surrogate test to find out whether retroviruses play a part in the development of primary biliary cirrhosis.

METHODS

We did western blot tests for HIV-1 and the human intracisternal A-type particle (HIAP), on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers.

FINDINGS

HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0.003). Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in four (17%) of those with other biliary diseases. None of the 23 patients with either alcohol-related liver disease or alpha1-antitrypsin deficiency, and only one of the healthy controls showed the same reactivity to HIAP proteins (p<0.0001). Our results showed a strong association between HIAP seroreactivity and the detection of autoantibodies to double-stranded DNA. HIAP seroreactivity was also strongly associated with the detection of mitochondrial, nuclear, and extractable nuclear antigens.

INTERPRETATION

The HIV-1 and HIAP antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses.

摘要

背景

逆转录病毒被认为与多种自身免疫性疾病的病因有关。我们使用免疫印迹作为替代检测方法,以查明逆转录病毒是否在原发性胆汁性肝硬化的发展中起作用。

方法

我们对77例原发性胆汁性肝硬化患者、126例慢性肝病患者、48例系统性红斑狼疮患者和25名健康志愿者的血清样本进行了针对HIV-1和人A型微粒(HIAP)的蛋白质印迹检测。

结果

在77例原发性胆汁性肝硬化患者中有27例(35%)、48例系统性红斑狼疮患者中有14例(29%)、28例慢性病毒性肝炎患者中有14例(50%)以及23例原发性硬化性胆管炎或胆道闭锁患者中有9例(39%)检测到HIV-1 p24 gag血清反应性,相比之下,24例酒精性肝病或α1-抗胰蛋白酶缺乏性肝病患者中只有1例(4%),25名健康志愿者中只有1例(4%)检测到该反应性(p=0.003)。在37例(51%)原发性胆汁性肝硬化患者、28例(58%)系统性红斑狼疮患者、15例(20%)慢性病毒性肝炎患者以及4例(17%)其他胆道疾病患者中发现针对两种以上HIAP蛋白的蛋白质印迹反应性。23例酒精性肝病或α1-抗胰蛋白酶缺乏患者中无一例,健康对照中只有1例对HIAP蛋白有相同反应性(p<0.0001)。我们的结果显示HIAP血清反应性与双链DNA自身抗体的检测之间存在强关联。HIAP血清反应性也与线粒体、核和可提取核抗原的检测密切相关。

解读

在原发性胆汁性肝硬化和其他胆道疾病患者中发现的HIV-1和HIAP抗体反应性可能归因于对抗原相关细胞蛋白的自身免疫反应,或归因于对与这些逆转录病毒共享抗原决定簇的未鉴定病毒蛋白的免疫反应。

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