The commonness in immune infiltration of rheumatoid arthritis and atherosclerosis: Screening for central targets via microarray data analysis

Abstract

BackgroundAlthough increasing evidence has reported an increased risk of atherosclerosis (AS) in rheumatoid arthritis (RA), the communal molecular mechanism of this phenomenon is still far from being fully elucidated. Hence, this article aimed to explore the pathogenesis of RA complicated with AS.MethodsBased on the strict inclusion/exclusion criteria, four gene datasets were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the communal differentially expressed genes (DEGs) and hub genes, comprehensive bioinformatics analysis, including functional annotation, co-expression analysis, expression validation, drug-gene prediction, and TF-mRNA-miRNA regulatory network construction, was conducted. Moreover, the immune infiltration of RA and AS was analyzed and compared based on the CIBERSORT algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in RA and AS respectively.ResultsA total of 54 upregulated and 12 downregulated communal DEGs were screened between GSE100927 and GSE55457, and functional analysis of these genes indicated that the potential pathogenesis lies in immune terms. After the protein-protein interaction (PPI) network construction, a total of six hub genes (CCR5, CCR7, IL7R, PTPRC, CD2, and CD3D) were determined as hub genes, and the subsequent comprehensive bioinformatics analysis of the hub genes re-emphasized the importance of the immune system in RA and AS. Additionally, three overlapping infiltrating immune cells were found between RA and AS based on the CIBERSORT algorithm, including upregulated memory B cells, follicular helper T cells and γδT cells.ConclusionsOur study uncover the communal central genes and commonness in immune infiltration between RA and AS, and the analysis of six hub genes and three immune cells profile might provide new insights into potential pathogenesis therapeutic direction of RA complicated with AS.

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

“…Monocytes as a type of circulation blood cells have been proven in many studies to relate to sarcopenia and osteoporosis ( Deng et al, 2021 ; Nie et al, 2022 ; Zeng et al, 2022 ). Consistent with previous studies used different kind of specimens ( Wang Z. et al, 2022 ; Liu J. et al, 2022 ; Mo et al, 2022 ), we have concluded that the intersection between gene expression maps of muscle tissues and monocytes may provide us much wider insights into the development of osteosarcopenia ( Liu et al, 2017 ). In our study, key crosstalk genes ( ARHGEF10 , PCDH7 , CST6 , and ROBO3 ) were identified by DEG analysis, WGCNA, and machine learning methods, and then validated by independent datasets and clinical samples.…”

Identification of common mechanisms and biomarkers for dermatomyositis and atherosclerosis based on bioinformatics analysis

“…In the etiology of AS, the chemokine receptor CXCR4 is notably present across a diverse range of cellular entities implicated in CVD, encompassing ECs, Vascular Smooth Muscle Cells (VSMCs), T-cells, B-cells, neutrophils, monocytes, and macrophages. 71 Investigations spearheaded by Merckelbach et al 96 have illuminated a marked upsurge in the transcriptional and protein concentrations of CXCR4 and CXCL12 within carotid atherosclerotic plaques, as contrasted with normative vascular structures. 97,98 Further substantiation from zoological research delineates CXCR4's contributory role in AS, evidencing that its augmented expression within murine cardiac tissue amplifies infarct dimensions, diminishes myocardial efficiency, and catalyzes the influx of pro-inflammatory cellular units.…”

“…In the etiology of AS, the chemokine receptor CXCR4 is notably present across a diverse range of cellular entities implicated in CVD, encompassing ECs, Vascular Smooth Muscle Cells (VSMCs), T‐cells, B‐cells, neutrophils, monocytes, and macrophages 71 . Investigations spearheaded by Merckelbach et al 96 .…”

“… 67 Nonetheless, a definitive association between PTPRC expression and DM progression remains to be established. In the context of AS, PTPRC's role as a central gene has been acknowledged, 69 , 70 , 71 , 72 , 73 particularly regarding its involvement in the disease's advancement through mechanisms linked to T‐cells regulatory, 74 a correlation further substantiated by experimental models in animals. 75 Hence, the augmented expression of PTPRC emerges as a critical factor for both DM and AS, underscoring the therapeutic potential of PTPRC inhibitors in mitigating the progression of these diseases.…”

Identification of the shared mechanisms and common biomarkers between Sjögren’s syndrome and atherosclerosis using integrated bioinformatics analysis

“…T regs maintain immune homeostasis by releasing immunosuppressive cytokines, including IL-10 and TGF-b, or directly inhibiting proinflammatory cytokine production from monocytes and macrophages. Thus, T reg cells play a protective role in AS, and their deficiency is associated with a significant increase in atherosclerotic lesions ( 34 ). Consistent with the previous conclusion, the immune infiltration analysis revealed a significantly decreased proportion of T reg cells in AS patients.…”