Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology

Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology
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原发性胆汁性肝硬化中的丙酮酸脱氢酶抗体:与组织学的相关性

DOI:
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发表时间:
1998
期刊:
Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS)
影响因子:
--
通讯作者:
R. Uibo
R. Uibo
中科院分区:
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文献类型:
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作者:
K. Kisand;K. Kisand;A. Karvonen;M. Vuoristo;J. Mattila;J. Mäkinen;R. Uibo

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丙酮酸脱氢酶的抗线粒体抗体是原发性胆汁性肝硬化的标志。尽管丙酮酸脱氢酶抗体与胆管上皮结合,但其致病作用尚未得到证实。本研究的目的是表征丙酮酸脱氢酶的血清 IgA 抗体并评估其对不同治疗方案的反应。我们还将抗体水平与组织学病变的严重程度以及生化肝脏测试的数据进行了比较。研究人员在基线时和 24 个月后从 61 名原发性胆汁性肝硬化患者中收集血清样本,其中 23 名患者接受熊去氧胆酸治疗,20 名患者接受秋水仙碱治疗,18 名患者接受安慰剂治疗。 ELISA用于检测丙酮酸脱氢酶抗体。 IgA 和 IgG 分别用 Jacalin 和 Protein-A 分离。通过分光光度法观察酶反应速率来检测免疫球蛋白抑制酶活性的能力。 61 名患者中有 49 名(80.3%)拥有丙酮酸脱氢酶 IgA 抗体。仅在熊去氧胆酸组中观察到 IgA 抗体显着降低(p7<0.05)。患者血清的 18 种 IgA 制剂中的 15 种和所有 24 种 IgG 制剂对丙酮酸脱氢酶具有抑制作用(平均抑制百分比±SD:在蛋白质浓度为 100 μg/ml 时分别为 42±33.4% 和 79±22.4%)。丙酮酸脱氢酶血清抗体水平与多种组织学参数(纤维化、炎症浸润)相关,但与生化参数无关。我们的数据表明,丙酮酸脱氢酶的 IgA 抗体会抑制酶的功能。丙酮酸脱氢酶抗体与组织学参数之间的相关性可能表明这些抗体的致病作用。
Antimitochondrial antibodies to pyruvate dehydrogenase are the hallmark of primary biliary cirrhosis. Their pathogenic role has not been proven, although antibodies to pyruvate dehydrogenase are bound to biliary epithelium. The aim of this study was to characterize serum IgA antibodies to pyruvate dehydrogenase and to evaluate their response to different treatment regimens. We also compared the level of antibodies with severity of histological lesions and the data of biochemical liver tests. Serum samples were collected at baseline and after 24 months from 61 primary biliary cirrhosis patients, whereas 23 patients were treated with ursodeoxycholic acid, 20 with colchicine, and 18 with placebo. ELISA was used to detect antibodies to pyruvate dehydrogenase. IgA and IgG were separated with jacalin and protein‐A, respectively. Capacity of immunoglobulins to inhibit enzymatic activity was detected by spectrophotometric observation of the rate of enzyme reaction. 49 (80.3%) of the 61 patients possessed IgA antibodies to pyruvate dehydrogenase. Significant decrease in IgA antibodies was observed only in the ursodeoxycholic acid group (p7<0.05). 15 of 18 IgA preparations and all 24 IgG preparations of patients' sera were inhibitory towards pyruvate dehydrogenase (mean inhibitory percent ±SD: 42±33.4% and 79±22.4%, respectively, at a protein concentration of 100 μg/ml). The level of serum antibodies to pyruvate dehydrogenase correlated with several histological parameters (fibrosis, inflammatory infiltrate), but not with biochemical parameters. Our data reveal that IgA antibodies to pyruvate dehydrogenase inhibit enzyme function. The correlation between antibodies to pyruvate dehydrogenase and histological parameters might suggest the pathogenic role of these antibodies.
原发性胆汁性肝硬化的抗线粒体抗体识别二氢硫辛酰胺酰基转移酶并抑制支链α-酮酸脱氢酶复合物的酶功能。
DOI: --
发表时间: 1989
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Fregeau,DR;Davis,PA;Danner,DJ;Ansari,A;Coppel,RL;Dickson,ER;Gershwin,ME
通讯作者: Gershwin,ME