Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for juvenile idiopathic arthritis

IF 4.7 Q2 IMMUNOLOGY Journal of Translational Autoimmunity Pub Date : 2024-10-26 DOI:10.1016/j.jtauto.2024.100256
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Abstract

Background

Juvenile idiopathic arthritis (JIA) is a prevalent chronic rheumatic disease affecting children. Current medications merely alleviate symptoms rather than curing the disease. Hence, the identification and development of novel drug targets and biomarkers for JIA are imperative for enhancing treatment efficacy.

Methods

We employed two-sample Mendelian randomization (MR) analysis to investigate the causal effects of plasma proteins on JIA. Additionally, colocalization, bulk RNA-seq, and single-cell RNA-seq analyses were conducted to further investigate and validate the potential of candidate proteins as drug targets.

Results

Through MR analysis, we successfully identified five plasma proteins that are causally linked to JIA. Genetically inferred lower levels of AIF1, TNF, and TNFSF11 were associated with an elevated risk of JIA, while higher levels of AGER and GP1BA proteins were positively correlated with JIA risk. Colocalization analysis further supported our findings on GP1BA (OR = 9.26, 95 % CI: 2.30–37.20) and TNFSF11 (OR = 0.18, 95 % CI: 0.07–0.45). Based on this evidence, we classified these five proteins into two tiers. Finally, we conducted a systematic evaluation of the druggability and current drug development progress for these identified candidate proteins.

Conclusions

This study employed MR analysis to reveal causal relationships between plasma proteins and JIA, identifying five potential candidate proteins as promising drug targets for JIA, particularly focusing on GP1BA and TNFSF11.
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综合分析多组学数据,发现幼年特发性关节炎的生物标记物和治疗靶点
背景青少年特发性关节炎(JIA)是一种影响儿童的流行性慢性风湿病。目前的药物只能缓解症状,而不能治愈疾病。因此,鉴定和开发JIA的新型药物靶点和生物标志物对于提高治疗效果势在必行。方法我们采用双样本孟德尔随机化(MR)分析法研究血浆蛋白对JIA的因果效应。结果通过MR分析,我们成功鉴定了5种与JIA有因果关系的血浆蛋白。根据基因推断,较低水平的AIF1、TNF和TNFSF11与JIA风险升高有关,而较高水平的AGER和GP1BA蛋白与JIA风险呈正相关。共定位分析进一步支持了我们对 GP1BA(OR = 9.26,95 % CI:2.30-37.20)和 TNFSF11(OR = 0.18,95 % CI:0.07-0.45)的研究结果。根据这些证据,我们将这五种蛋白质分为两级。结论 本研究采用磁共振分析揭示了血浆蛋白与 JIA 之间的因果关系,确定了五种潜在的候选蛋白作为治疗 JIA 的有希望的药物靶点,尤其关注 GP1BA 和 TNFSF11。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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