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血清笼蛋白抗体水平在假性剥脱性青光眼患者中降低。

Serological Levels of Anti-clathrin Antibodies Are Decreased in Patients With Pseudoexfoliation Glaucoma.

机构信息

Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

出版信息

Front Immunol. 2021 Feb 19;12:616421. doi: 10.3389/fimmu.2021.616421. eCollection 2021.

Abstract

Evidence for immunologic contribution to glaucoma pathophysiology is steadily increasing in ophthalmic research. Particularly, an altered abundance of circulating autoantibodies to ocular antigens is frequently observed. Here, we report an analysis of autoantibody abundancies to selected antigens in sera of open-angle glaucoma patients, subdivided into normal-tension glaucoma ( = 31), primary open-angle glaucoma ( = 43) and pseudoexfoliation glaucoma ( = 45), vs. a non-glaucomatous control group ( = 46). Serum samples were analyzed by protein microarray, including 38 antigens. Differences in antibody levels were assessed by ANOVA. Five serological antibodies showed significantly altered levels among the four groups ( < 0.05), which can be used to cluster the subjects in groups consisting mainly of PEXG or POAG/NTG samples. Among the altered autoantibodies, anti-Clathrin antibodies were identified as most important subgroup predictors, enhancing prospective glaucoma subtype prediction. As a second aim, we wanted to gain further insights into the characteristics of previously identified glaucoma-related antigens and their role in glaucoma pathogenesis. To this end, we used the bioinformatics toolset of Metascape to construct protein-protein interaction networks and GO enrichment analysis. Glaucoma-related antigens were significantly enriched in 13 biological processes, including mRNA metabolism, protein folding, blood coagulation and apoptosis, proposing a link of glaucoma-associated pathways to changes in the autoantibody repertoire. In conclusion, our study provides new aspects of the involvement of natural autoimmunity in glaucoma pathomechanisms and promotes advanced opportunities toward new diagnostic approaches.

摘要

越来越多的眼科研究证据表明,免疫因素参与了青光眼的病理生理学过程。特别是,经常观察到循环自身抗体对眼部抗原的丰度发生改变。在这里,我们报告了对开角型青光眼患者血清中选定抗原的自身抗体丰度的分析,这些患者分为正常眼压性青光眼(n = 31)、原发性开角型青光眼(n = 43)和假性剥脱性青光眼(n = 45),以及非青光眼对照组(n = 46)。通过蛋白质微阵列分析血清样本,包括 38 种抗原。通过方差分析评估抗体水平的差异。五种血清抗体在四组之间显示出明显改变的水平(<0.05),这可以用于将主要由 PEXG 或 POAG/NTG 样本组成的组中的受试者进行聚类。在改变的自身抗体中,鉴定出抗网格蛋白抗体为最重要的亚组预测因子,增强了对青光眼亚型的预测。作为第二个目标,我们希望进一步了解先前鉴定出的与青光眼相关的抗原的特征及其在青光眼发病机制中的作用。为此,我们使用 Metascape 的生物信息学工具集构建蛋白质-蛋白质相互作用网络和 GO 富集分析。与青光眼相关的抗原在 13 个生物学过程中显著富集,包括 mRNA 代谢、蛋白质折叠、血液凝固和细胞凋亡,这表明青光眼相关途径与自身抗体库的变化之间存在联系。总之,我们的研究为自然自身免疫在青光眼发病机制中的参与提供了新的方面,并为新的诊断方法提供了更多的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b37/7933590/963f3b41e20b/fimmu-12-616421-g0001.jpg

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