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乳酸化相关基因作为类风湿关节炎诊断和免疫浸润的潜在标志物。

Lactylation-related genes serve as potential markers for the diagnosis and immune infiltration in rheumatoid arthritis.

作者信息

Liu Chunhua, Zheng Jianxiong, Hao Jiayao, Kang Wenjiao, Mao Jing, Hu Caiyun, Ouyang Yuhong, Shen Haili

机构信息

Department of Rheumatology, Lanzhou University Second Hospital, Lanzhou, China.

The Second Clinical Medical College, Lanzhou University, Lanzhou, China.

出版信息

Autoimmunity. 2025 Dec;58(1):2474217. doi: 10.1080/08916934.2025.2474217. Epub 2025 Mar 6.

DOI:10.1080/08916934.2025.2474217
PMID:40048636
Abstract

Lactylation is widely involved in cellular processes and is pivotal in inflammation and immune regulation. However, the expression and clinical significance of lactylation in rheumatoid arthritis (RA) remain unclear. This study aimed to determine the role of lactylation in RA and its association with immune cell infiltration. We initially detected the levels of lactate in the plasma of RA patients and the levels of panlysine lactylation (Pan-Kla) in peripheral blood mononuclear cells (PBMCs). Next, we used differential expression analysis and weighted gene coexpression network analysis (WGCNA) to intersect with lactylation-related genes. We obtained lactylation-related differentially expressed genes (LADEGs) in RA and analyzed their functional enrichment. We subsequently used the CIBERSORT algorithm to analyze immune cell infiltration in RA synovial tissues and its correlation with LADEGs. Finally, key genes of LADEGs were validated in the Pathobiology of Early Arthritis Cohort (PEAC) study and our samples. Our study revealed elevated levels of lactate and lactylation in the peripheral blood of RA patients. IKAROS family zinc finger 1 (IKZF1), lymphocyte cytosolic protein 1 (LCP1), and WASP actin-nucleation promoting factor (WAS) may be potential biomarkers for early diagnosis and assessment of disease activity in RA.

摘要

乳酰化广泛参与细胞过程,在炎症和免疫调节中起关键作用。然而,乳酰化在类风湿关节炎(RA)中的表达及临床意义仍不清楚。本研究旨在确定乳酰化在RA中的作用及其与免疫细胞浸润的关联。我们首先检测了RA患者血浆中的乳酸水平以及外周血单个核细胞(PBMCs)中的全赖氨酸乳酰化(Pan-Kla)水平。接下来,我们使用差异表达分析和加权基因共表达网络分析(WGCNA)与乳酰化相关基因进行交叉分析。我们获得了RA中与乳酰化相关的差异表达基因(LADEGs)并分析了它们的功能富集情况。随后,我们使用CIBERSORT算法分析RA滑膜组织中的免疫细胞浸润及其与LADEGs的相关性。最后,在早期关节炎队列病理生物学(PEAC)研究和我们的样本中验证了LADEGs的关键基因。我们的研究揭示了RA患者外周血中乳酸和乳酰化水平升高。IKAROS家族锌指蛋白1(IKZF1)、淋巴细胞胞质蛋白1(LCP1)和WASP肌动蛋白成核促进因子(WAS)可能是RA早期诊断和疾病活动评估的潜在生物标志物。

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