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糖皮质激素和托法替布治疗后与大动脉炎相关的生物标志物变化和分子特征

Biomarker Changes and Molecular Signatures Associated with Takayasu Arteritis Following Treatment with Glucocorticoids and Tofacitinib.

作者信息

Dai Xiaojuan, Wang Jinghua, Zhang Xiao, Wang Li, Wu Sifan, Chen Huiyong, Sun Ying, Ma Lili, Ma Lingying, Kong Xiufang, Jiang Lindi

机构信息

Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, People's Republic of China.

出版信息

J Inflamm Res. 2022 Aug 3;15:4395-4407. doi: 10.2147/JIR.S369963. eCollection 2022.

DOI:10.2147/JIR.S369963
PMID:35945989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9357419/
Abstract

OBJECTIVE

This study aimed to analyze biomarker changes in patients with TAK following treatment with glucocorticoids (GCs) and tofacitinib (TOF).

METHODS

Seventeen patients from a prospective TAK cohort treated with GCs and TOF and 12 healthy individuals were recruited. TAK associated cytokines, chemokines, growth factors, and MMPs were analyzed in these patients before and after GCs and TOF treatment, and healthy controls. Molecular signatures associated with clinical features were evaluated.

RESULTS

Patients' cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factors (VEGF), and MMP9 levels were significantly higher at baseline (all p < 0.05), while patients' FGF-2 levels were significantly lower (p = 0.02). After treatment, IL-10 was significantly increased at 6 months (p=0.007), and inflammatory cytokines such as PTX3, IL-6 demonstrated a downward trend. Patients without vascular occlusion had higher baseline CCL22 levels than patients with it (p = 0.05), which remained persistently higher after treatment. Radar plot analysis demonstrated that PTX3 was closely correlated with disease activity. In addition, patients without imaging improvement had relatively higher baseline levels of CCL22, FGF-2, and PDGF-AB (p = 0.056, p = 0.06 and p = 0.08 respectively) and lower baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively) compared with patients without it.

CONCLUSION

GCs and TOF are effective in decreasing inflammatory molecules but have limited efficacy in regulating multiple other markers involved in TAK. PTX3 is a prominent marker for disease activity, and CCL22 may have a predictive value for vascular progression.

摘要

目的

本研究旨在分析大动脉炎(TAK)患者接受糖皮质激素(GCs)和托法替布(TOF)治疗后的生物标志物变化。

方法

招募了17名接受GCs和TOF治疗的前瞻性TAK队列患者以及12名健康个体。对这些患者在接受GCs和TOF治疗前后以及健康对照者进行TAK相关细胞因子、趋化因子、生长因子和基质金属蛋白酶(MMPs)分析。评估与临床特征相关的分子特征。

结果

患者的细胞因子(PTX3、IL-6、IFN-γ)、趋化因子(IL-16、CCL22、CCL2)、生长因子(VEGF)和MMP9水平在基线时显著更高(均p<0.05),而患者的FGF-2水平显著更低(p = 0.02)。治疗后,IL-10在6个月时显著升高(p = 0.007),并且诸如PTX3、IL-6等炎性细胞因子呈下降趋势。无血管闭塞的患者基线CCL22水平高于有血管闭塞的患者(p = 0.05),治疗后仍持续较高。雷达图分析表明PTX3与疾病活动密切相关。此外,与影像学有改善的患者相比,影像学无改善的患者基线时CCL22、FGF-2和PDGF-AB水平相对较高(分别为p = 0.056、p = 0.06和p = 0.08),而TNFα、ESR和CRP基线水平较低(分别为p = 0.04、p = 0.056、p = 0.07)。

结论

GCs和TOF在降低炎性分子方面有效,但在调节TAK涉及的多种其他标志物方面疗效有限。PTX3是疾病活动的一个突出标志物,并且CCL22可能对血管进展具有预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/06191cbff597/JIR-15-4395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/67a91ebb435b/JIR-15-4395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/5f8535d833bf/JIR-15-4395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/eedd1954c2b7/JIR-15-4395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/06191cbff597/JIR-15-4395-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/67a91ebb435b/JIR-15-4395-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/5f8535d833bf/JIR-15-4395-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/eedd1954c2b7/JIR-15-4395-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8530/9357419/06191cbff597/JIR-15-4395-g0004.jpg

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Ann Rheum Dis. 2022 Jan;81(1):117-123. doi: 10.1136/annrheumdis-2021-220832. Epub 2021 Aug 6.
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Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms.
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Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.Pentraxin 3 比 C 反应蛋白更能准确评估 Takayasu 动脉炎的活动度:系统评价和荟萃分析。
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