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全球蛋白质组学分析揭示了新发病强直性脊柱炎患者免疫调节异常。

Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis.

机构信息

Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, China.

出版信息

Front Immunol. 2022 Mar 17;13:838891. doi: 10.3389/fimmu.2022.838891. eCollection 2022.

Abstract

BACKGROUND

Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients.

MATERIAL AND METHODS

Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis.

RESULTS

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients.

CONCLUSION

The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.

摘要

背景

强直性脊柱炎(AS)是一种慢性炎症性疾病,后果严重,发病率和死亡率高。在我们之前的工作中,我们揭示了新发病强直性脊柱炎患者蛋白质的关键特征。

材料和方法

强直性脊柱炎(AS)是一种影响脊柱的慢性炎症性疾病,炎症在 AS 的发病机制中起着至关重要的作用。然而,由于其复杂性,AS 中的炎症过程仍知之甚少。我们使用系统的蛋白质组学和磷酸化分析外周血单核细胞(PBMC)来研究参与 AS 发病机制的潜在途径。

结果

进行了液相色谱-串联质谱(LC-MS/MS)分析,发现 9 例新发病强直性脊柱炎患者和 9 例健康对照者之间有 782 个差异表达蛋白(DEPs)和 122 个差异磷酸化蛋白(DPPs)。使用平行反应监测(PRM)分析进一步验证了 DEPs。PRM 分析验证了抗原处理和呈递途径中的 3 种蛋白(HSP90AB1、HSP90AA1 和 HSPA8)、血小板激活途径中的 6 种蛋白(包括 ITPR1、MYLK 和 STIM1)和白细胞跨内皮迁移途径中的 10 种蛋白(包括 MYL12A、MYL9 和 ROCK2)在 AS 患者的 PBMC 中高表达。

结论

参与抗原处理和呈递、血小板激活和白细胞跨内皮迁移的关键蛋白揭示了新发病强直性脊柱炎患者的异常免疫调节。这些蛋白可能作为 AS 诊断和新治疗靶点的候选标志物,以及阐明 AS 的病理生理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abfd/8967996/1d7bc93045de/fimmu-13-838891-g001.jpg

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