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阿尔茨海默病患者脑脊液和血清中抗卵清蛋白抗体浓度升高——关于人类丝氨酸蛋白酶抑制剂的相似性及其可能参与疾病机制的讨论

Increased Concentration of Anti-Egg Albumin Antibodies in Cerebrospinal Fluid and Serum of Patients with Alzheimer's Disease-Discussion on Human Serpins' Similarity and Probable Involvement in the Disease Mechanism.

作者信息

Amanatidou Dionysia, Tsolaki Magdalini, Fouskas Vasileios, Gavriilidis Ioannis, Myriouni Maria, Anastasiou Anna, Papageorgiou Efthimia, Porfyriadou Diona, Parcharidi Zoi, Papasavva Eleftheria, Fili Maria, Eleftheriou Phaedra

机构信息

School of Health, Department of Biomedical Sciences, International Hellenic University, Sindos, 57400 Thessaloniki, Greece.

Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation (CIRI-AUTh), Balkan Center, Aristotle University of Thessaloniki, Building A, 57001 Thessaloniki, Greece.

出版信息

Biomolecules. 2025 Jul 27;15(8):1085. doi: 10.3390/biom15081085.

Abstract

Alzheimer's Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood-brain barrier (BBB) penetration, observed in AD, may facilitate immunologic response to food-derived antigens. In the present study, antibodies against egg albumin, bovine-casein, and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients using an enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentrations of anti-casein antibodies were detected. Increased anti-native egg albumin antibodies were present in the serum of patients of all stages with 65% positivity ( < 0.001) in mild disease and a higher percentage in females (81.9%, < 0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed, showing a gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen, reaching 61.8% in severe vs. 15% in mild disease ( < 0.001). Increased values were mainly observed in males. Anti-egg albumin antibodies may be implicated in the disease mechanism through sequence/structural similarity with human proteins, mainly serpins, and it would be worth consideration in further investigations and therapeutic strategies.

摘要

阿尔茨海默病(AD)是一个多因素过程。淀粉样斑块形成是该疾病的主要特征。尽管已确定了许多与AD相关的因素,但在几个方面其机制仍不清楚。在AD中观察到的肠道和血脑屏障(BBB)通透性紊乱可能会促进对食物源性抗原的免疫反应。在本研究中,使用酶联免疫吸附测定(ELISA)检测了患者脑脊液(CSF)和血清中针对卵清蛋白、牛酪蛋白和N-羟乙酰神经氨酸(Neu5Gc)的抗体。未检测到抗Neu5Gc抗体,且抗酪蛋白抗体浓度较低。在所有阶段患者的血清中均存在抗天然卵清蛋白抗体增加的情况,轻度疾病患者的阳性率为65%(<0.001),女性的阳性率更高(81.9%,<0.001)。观察到抗变性卵清蛋白抗体的血清阳性率较低,且随着疾病严重程度逐渐增加,女性中的患病率也更高。在脑脊液中,抗天然和抗变性卵清蛋白抗体主要在重症患者中观察到,对任何一种抗原的累积阳性率,重症患者为61.8%,轻度疾病患者为15%(<0.001)。升高的值主要在男性中观察到。抗卵清蛋白抗体可能通过与人类蛋白质(主要是丝氨酸蛋白酶抑制剂)的序列/结构相似性参与疾病机制,这在进一步研究和治疗策略中值得考虑。

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