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抗血管舒张刺激磷蛋白(VASP)抗体与系统性红斑狼疮中的神经精神障碍相关。

Anti-vasodilator-stimulated phosphoprotein (VASP) antibodies are associated with neuropsychiatric disorders in systemic lupus erythematosus.

作者信息

Zhu Chenxi, Liu Yan, Xu Jiayi, Yang Hang, Zhao Yi, Liu Yi

机构信息

Department of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Heliyon. 2024 Aug 31;10(17):e37110. doi: 10.1016/j.heliyon.2024.e37110. eCollection 2024 Sep 15.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies, pathogenic factors that can serve as diagnostic biomarkers. The current research has been focusing on exploring specific autoantigens with clinical relevance for SLE subtypes. In line with this objective, this study investigated potential antigenic targets associated with specific phenotypes in SLE by leveraging an omics-based approach combined with immunoassay techniques.

METHODS

A transcriptomic analysis was conducted in a cohort of 70 SLE patients to identify genes significantly correlated to the relevant phenotype. Epitope mapping and sequence analysis techniques were used to predict autoantigens, and the corresponding antibodies were subsequently quantified by enzyme-linked immunosorbent assay (ELISA) and validated by Western blot.

RESULTS

Transcriptomic data analysis revealed a group of hub genes exhibiting a significant correlation with the neuropsychiatric phenotype and a positive relationship with platelets. Subsequent epitope prediction for the corresponding proteins highlighted vasodilator-stimulated phosphoprotein (VASP) as a potential autoantigen. Moreover, ELISA and immunoblotting confirmed that the anti-VASP antibody present in the serum was significantly elevated in SLE patients with neuropsychiatric involvement and positively associated with demyelination.

CONCLUSION

VASP harbors autoantigenic epitopes associated with neuropsychiatric phenotype, especially the demyelination symptom in SLE, and its antibodies may serve as promising biomarkers in this disease.

摘要

背景

系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,其特征为多器官受累以及存在自身抗体,这些致病因素可作为诊断生物标志物。目前的研究一直聚焦于探索与SLE亚型具有临床相关性的特定自身抗原。为实现这一目标,本研究通过利用基于组学的方法结合免疫测定技术,调查了与SLE特定表型相关的潜在抗原靶点。

方法

对70例SLE患者进行转录组分析,以鉴定与相关表型显著相关的基因。采用表位作图和序列分析技术预测自身抗原,随后通过酶联免疫吸附测定(ELISA)对相应抗体进行定量,并通过蛋白质印迹法进行验证。

结果

转录组数据分析揭示了一组与神经精神表型显著相关且与血小板呈正相关的枢纽基因。对相应蛋白质的后续表位预测突出显示血管舒张刺激磷蛋白(VASP)为潜在的自身抗原。此外,ELISA和免疫印迹证实,神经精神受累的SLE患者血清中存在的抗VASP抗体显著升高,且与脱髓鞘呈正相关。

结论

VASP含有与神经精神表型相关的自身抗原表位,尤其是SLE中的脱髓鞘症状,其抗体可能是该疾病中有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c27a/11407959/9ce58cc8ca5e/gr1.jpg

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