Integrative Transcriptomic Analysis of Peripheral Blood Monocytes in Systemic Sclerosis and Shared Pathogenic Pathways in Autoimmune Diseases

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Shaoqi Chen , Yu Fan , Qiulin Wu , Guohong Zhang , Yukai Wang , Weiping Li , Shengli Yang , Marco Matucci-Cerinic , Daniel E. Furst
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引用次数: 0

Abstract

Background

Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs.

Methods

RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs.

Results

1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response.

DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p < 0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis.

Conclusions

This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.

系统性硬化症患者外周血单核细胞的转录组整合分析与自身免疫性疾病的共同致病途径
背景系统性硬化症(SSc)是一种自身免疫性疾病(AD),与类风湿性关节炎(RA)、系统性红斑狼疮(SLE)和原发性斯约格伦综合征(pSS)相比,它受到的关注较少。本研究旨在分析 SSc 患者外周血单核细胞(PBMC)与其他 ADs 相比的转录特征和免疫细胞组成。方法分析了 119 名未经治疗的患者(8 名 SSc 患者、42 名 RA 患者、41 名 pSS 患者、28 名 SLE 患者)和 20 名健康对照的 RNA-seq 数据。结果 在 SSc 中发现了 1,148 个 DEGs,上调的基因与巨核细胞过程有关,下调的基因与中性粒细胞功能和免疫反应有关。上调的转录因子(TFs)与胚胎造血有关,下调的TFs参与白细胞分化和免疫调节。与其他 ADs 的比较分析显示了共同的致病途径,强调了巨核细胞的增殖。与健康对照组相比,ADs 中的中性粒细胞数量明显减少(p < 0.001)。比较分析强调了常见的发病途径,尤其是巨核细胞增殖,以及 SSc 中的独特基因(MEGF9、MMP8 和 KRT 家族成员),表明这些基因在中性粒细胞功能、皮肤完整性和纤维化中的作用。结论这项研究发现了 SSc 中与中性粒细胞功能和巨核细胞增加有关的基因表达失调(KRT 和 MMP8),强调了自身免疫性疾病的共同模式。这些发现为了解 SSc 的潜在发病机制提供了新的视角,有助于探索治疗的新靶点。
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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
期刊介绍: Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.
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