Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic
Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic
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DOI：
10.1002/hep.20788
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发表时间：
2005-08-01
期刊：
影响因子：
13.5
通讯作者：
Vergani, D
中科院分区：
文献类型：
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作者：
Bogdanos, DP;Baum, H;Vergani, D
原发性胆汁性肝硬化（PBC）的血清学标志是丙酮酸脱氢酶复合物E2亚单位（PDC-E2）抗线粒体抗体（AMA）的存在。抗PDC-E2抗体与分枝杆菌hsp 65特异性交叉反应，并且我们已经证明PDC-E2（212-226）和hsp共享的基序SxGDL[ILV]AE是交叉反应性靶标。已经发现该相同的基序仅存在于德氏乳杆菌的β-半乳糖苷酶（BGAL LACDE）中，我们假设该同源性也将导致交叉反应性。通过ELISA检测模拟物的反应性和竞争性交叉反应性，使用来自100名AMA阳性和23名AMA阴性PBC患者和190名对照的血清。大肠杆菌（ECOLI）PDC-E2模拟物，已与PBC的致病性，但缺乏这个基序也进行了测试。抗BGAL 266 -280 1ACDE抗体仅限于AMA阳性患者（54/95，57%），属于免疫球蛋白（IG）G3。在190例对照中，22例（12%; P <0.001）具有抗BGAL 266 -280抗体，主要为IgG 4亚类。ECOLI PDC-E2反应性几乎不存在。IgG 3同种型的BGAL 266 -280/PDC-E2212-226反应性在52例（52%）AMA阳性PBC患者中发现，但仅在1例对照中发现（P < .001）。LACDE BGAL 266 -280/PDC-E2212-226的反应性是由于交叉反应性，如通过竞争ELISA所证实的。抗体对BGAL 26 G-280的亲和力大于对PDC-E2模拟物的亲和力。多反应性血清与BGAL 266 -280预孵育可使酶活性抑制降低40%，而在人或ECOLI PDC-E2模拟物中观察到边际效应（12%）或无效应（2%）。总之，BGAL LACDE的IgG 3抗体与主要线粒体自身表位交叉反应，是PBC的特征。
The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2(212-226) and hsp's is a cross-reactive target. Having found that this same motif is present only in beta-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL266-280 1ACDE antibodies were restricted to AMA-positive patients (54 of 95, 57 %) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12 %; P < .001) had anti-BGAL266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL266-280/PDC-E2212-226 reactivity of the IgG3 isotype was found in 52 (52 %) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL266-280/PDC-E2212-226 reactivity was due to cross-reactivity as confirmed via competition ELISA. Antibody affinity for BGAL26G-280 Was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL266-280 reduced the inhibition of enzymatic activity by 40 %, while marginal effect (12 %) or no effect (2 %) was observed in human or ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.