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PDC-E2 的催化结构域包含原发性胆汁性肝硬化中抗线粒体抗体识别的表位。

Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.

机构信息

Department of Internal Medicine II, University of Tuebingen, Otfried-Muller-Str. 10, 72076 Tuebingen, Germany.

出版信息

World J Gastroenterol. 2010 Feb 28;16(8):973-81. doi: 10.3748/wjg.v16.i8.973.

DOI:10.3748/wjg.v16.i8.973
PMID:20180236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2828602/
Abstract

AIM

To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC).

METHODS

Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore, the inner lipoyl peptide 167-184 was used in an unlipoylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA positive PBC patients, 63 patients with other liver disorders and 22 healthy blood donors served as controls.

RESULTS

Of the 95 PBC-sera, 74% reacted with the peptide 475-499 and 58% with the peptide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylated and lipoylated peptide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera, respectively; using ovalbumin-coupled peptides, the incidence increased up to 57% (unlipoylated form).

CONCLUSION

Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodominant epitopes recognized by AMA in PBC.

摘要

目的

寻找原发性胆汁性肝硬化(PBC)患者抗线粒体抗体(AMA)识别的丙酮酸脱氢酶复合体 E2 成分(PDC-E2)的进一步免疫显性肽。

方法

采用酶联免疫吸附试验,用 33 种合成的重叠肽(25 个氨基酸;aa)检测 95 例 PBC 患者血清,该肽覆盖 PDC-E2 E2 亚基的全长。此外,还使用非脂化和脂化形式以及与卵清蛋白偶联的内脂酰肽 167-184。11 例 AMA 阴性/ANA 阳性 PBC 患者、63 例其他肝病患者和 22 名健康献血者的血清作为对照。

结果

95 例 PBC 血清中,74%与位于 PDC-E2 催化结构域内的肽 475-499 反应,58%与肽 407-431 反应。其他疾病患者或健康对照者的阳性率最高为 18%。只有 5%和 11%的 PBC 血清中存在内脂酰域中非脂化和脂化的肽 167-184 抗体,使用卵清蛋白偶联肽,发病率增加到 57%(非脂化形式)。

结论

PDC-E2 催化结构域内的肽而不是先前报道的脂酰结合肽 167-184 可能代表 PBC 中 AMA 识别的主要免疫显性表位。

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