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针对波兰原发性胆汁性胆管炎患者血清中细菌抗原的抗体。

Antibodies directed against bacterial antigens in sera of Polish patients with primary biliary cholangitis.

作者信息

Bauer Alicja, Habior Andrzej

机构信息

Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland.

Clinic of Polish Gastroenterology Foundation, Warsaw, Poland.

出版信息

Front Cell Infect Microbiol. 2025 Jan 7;14:1410282. doi: 10.3389/fcimb.2024.1410282. eCollection 2024.

Abstract

BACKGROUND

Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease with the presence of characteristic autoantibodies. The aim of the work was to determine the level of antibodies directed against bacterial antigens: (anti-anti), (anti-), (anti- ) and () in sera of PBC patients. We also performed studies on the impact of the bacterial peptides on the specific antigen-antibody binding.

METHOD

We screened 92 Polish PBC patients and sera samples from healthy donors and pathological controls. Autoantibodies and anti-bacterial antibodies were determined by commercially available ELISA kits. Specific inhibition of antibody binding was also detected by the in house ELISA method.

RESULTS

Anti-, anti-, anti-, anti- and anti- antibodies were significantly more common in the group of PBC patients than in the pathological and healthy control groups: 74%, 40%, 84%, 39% and 69% respectively. The mean level of anti-, anti- , anti- anti- in the PBC group was significantly higher than those in the healthy group ( < 0.001). and in patients with other liver diseases. In sera of patients with the presence of positive anti-mitochondrial antibodies (AMA), specific for PBC, anti-bacterial antibodies have been found in 80% vs. 50% in sera with AMA negative. We observed inhibition of specific antigen-antibody binding by the bacterial peptide: EClpP ( caseinolytic protease) and adenine glycosylase from caseinolytic protease P, ClpP from peptide of , PDC from peptide and adenine glycosylase of . Bacterial factors influence the specific binding of antibodies to pyruvate dehydrogenase (PDC-E2), gp210 and KLHL12 (kelch-like peptide 12) antigens.

CONCLUSION

Microbial mimics may be the major targets of cross-reactivity with human pyruvate dehydrogenase, gp210, and KLHL12 in PBC.

摘要

背景

原发性胆汁性胆管炎(PBC)是一种胆汁淤积性自身免疫性肝病,存在特征性自身抗体。本研究的目的是测定PBC患者血清中针对细菌抗原的抗体水平:(抗 - )、(抗 - )、(抗 - )和()。我们还进行了关于细菌肽对特异性抗原 - 抗体结合影响的研究。

方法

我们筛选了92例波兰PBC患者以及来自健康供体和病理对照的血清样本。通过市售ELISA试剂盒测定自身抗体和抗细菌抗体。还通过内部ELISA方法检测抗体结合的特异性抑制。

结果

抗 - 、抗 - 、抗 - 、抗 - 和抗 - 抗体在PBC患者组中比在病理和健康对照组中更为常见:分别为74%、40%、84%、39%和69%。PBC组中抗 - 、抗 - 、抗 - 、抗 - 的平均水平显著高于健康组(<0.001)以及其他肝病患者。在存在PBC特异性的抗线粒体抗体(AMA)阳性的患者血清中,80%发现了抗细菌抗体,而AMA阴性血清中这一比例为50%。我们观察到细菌肽:EClpP(酪蛋白水解蛋白酶)和来自酪蛋白水解蛋白酶P的腺嘌呤糖基化酶、来自肽的ClpP、来自肽的PDC以及的腺嘌呤糖基化酶对特异性抗原 - 抗体结合有抑制作用。细菌因子影响抗体与丙酮酸脱氢酶(PDC - E2)、gp210和KLHL12(kelch样肽12)抗原的特异性结合。

结论

在PBC中,微生物模拟物可能是与人丙酮酸脱氢酶、gp210和KLHL12交叉反应的主要靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0f6/11752878/549fd2d25b51/fcimb-14-1410282-g001.jpg

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