Innovate therapeutic targets for autoimmune diseases: insights from proteome-wide mendelian randomization and Bayesian colocalization.

IF 3.3 4区医学 Q3 IMMUNOLOGY

Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-03-22 DOI:10.1080/08916934.2024.2330392

Qiubai Jin, Feihong Ren, Ping Song

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引用次数: 0

Abstract

Background: Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches.

Research design and methods: Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein-protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings.

Results: This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (p = 1.61E - 07). TYMP (p = 6.28E - 06) was identified as a protective factor for ulcerative colitis. For Crohn's disease, ERAP2 (p = 4.47E - 14), HP (p = 2.08E - 05), and RSPO3 (p = 6.52E - 07), were identified as facilitators, whereas FLRT3 (p = 3.42E - 07) had a protective effect. In rheumatoid arthritis, SWAP70 (p = 3.26E - 10), SIGLEC6 (p = 2.47E - 05), ISG15 (p = 3.69E - 05), and FCRL3 (p = 1.10E - 10) were identified as risk factors. B4GALT1 (p = 6.59E - 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (p = 1.58E - 09) but a risk factor for T1D (p = 7.36E - 11), respectively. External validation supported the associations of eight of these proteins with three ADs.

Conclusions: Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.

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自身免疫性疾病的创新治疗靶点：全蛋白质组亡羊补牢随机化和贝叶斯共定位的启示。

背景：尽管人们对自身免疫性疾病（ADs）发病机制的了解越来越多，但目前的治疗效果仍不理想。本研究旨在通过各种分析方法确定自身免疫性疾病的创新治疗靶点：利用孟德尔随机化、贝叶斯共定位、表型扫描和蛋白-蛋白相互作用网络，我们探索了14种AD的潜在治疗靶点，并从外部验证了我们的初步发现：结果：这项研究确定了12种循环蛋白作为6种AD的潜在治疗靶点。具体来说，IL12B 被判定为强直性脊柱炎的风险因素（p = 1.61E - 07）。TYMP（p = 6.28E - 06）被认为是溃疡性结肠炎的保护因素。对于克罗恩病，ERAP2（p = 4.47E - 14）、HP（p = 2.08E - 05）和 RSPO3（p = 6.52E - 07）被确定为促进因素，而 FLRT3（p = 3.42E - 07）则具有保护作用。在类风湿性关节炎中，SWAP70（p = 3.26E - 10）、SIGLEC6（p = 2.47E - 05）、ISG15（p = 3.69E - 05）和 FCRL3（p = 1.10E - 10）被确定为风险因素。有趣的是，CTSH分别被确定为嗜睡症的保护因素（p = 1.58E - 09）和T1D的风险因素（p = 7.36E - 11）。外部验证支持其中8种蛋白质与3种注意力缺失症有关：我们的综合研究发现了12种潜在的注意力缺失症治疗靶点，为未来注意力缺失症的药物开发提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autoimmunity 医学-免疫学

CiteScore

5.70

自引率

8.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.