Bauer Alicja, Habior Andrzej
Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland.
Clinic of Polish Gastroenterology Foundation, Warsaw, Poland.
Front Cell Infect Microbiol. 2025 Jan 7;14:1410282. doi: 10.3389/fcimb.2024.1410282. eCollection 2024.
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.
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.
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.
Microbial mimics may be the major targets of cross-reactivity with human pyruvate dehydrogenase, gp210, and KLHL12 in PBC.
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。
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。
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。
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。