AUTHOR=Wang Yimin , Su Wenge , Li Yunlun , Yuan Jie , Yao Minghao , Su Xiaoyi , Wang Yifei 

TITLE=Analyzing the pathogenesis of systemic lupus erythematosus complicated by atherosclerosis using transcriptome data

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.935545

DOI=10.3389/fimmu.2022.935545

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Accumulating evidence supports the predisposition of systemic lupus erythematosus (SLE) to atherosclerosis (AS). However, the common pathogenesis of these two diseases remains unclear. This study aimed to explore the mechanisms of SLE complicated by AS.</p></sec><sec><title>Methods</title><p>Gene expression profiles of SLE (GSE50772) and AS (GSE100927) were downloaded from the Gene Expression Omnibus. We analyzed differentially expressed genes (DEGs) of SLE and AS and performed enrichment analyses separately. After analyzing the common DEGs (CDEGs), we performed functional enrichment analysis, protein-protein interaction (PPI) network analysis, and hub genes (HGs) identification of CDEGs. Then, we performed a co-expression analysis of HGs and verified their expression and diagnostic value. We further explored immune cell infiltration and analyzed the correlation between HGs and infiltrating immune cells (IICs). Finally, we verified the reliability of the screening pathway.</p></sec><sec><title>Results</title><p>We obtained 530 DEGs from the GSE50772 dataset and 448 DEGs from the GSE100927 dataset. The results of the enrichment analysis showed that there were many similar immune- and inflammation-related processes between the two diseases. We analyzed 26 CDEGs (two downregulated genes and 24 upregulated genes) and enrichment analysis highlighted the important role of the IL-17 signaling pathway. We identified five HGs (<italic>CCR1</italic>, <italic>CD163</italic>, <italic>IL1RN</italic>, <italic>MMP9</italic>, and <italic>SIGLEC1</italic>) using the CytoHubba plugin and HGs validation showed that the five HGs screened were reliable. Co-expression networks showed that five HGs can affect mononuclear cell migration. Immune cell infiltration analysis indicated monocytes in SLE and M0 macrophages in AS accounted for a high proportion of all IICs, and the difference in infiltration was obvious. We also found a significant positive correlation between <italic>CCR1</italic>, <italic>CD163</italic>, <italic>IL1RN</italic>, and <italic>MMP9</italic> and monocytes in SLE, and a significant positive correlation between <italic>CCR1</italic>, <italic>IL1RN</italic>, <italic>MMP9</italic>, and <italic>SIGLEC1</italic> and M0 macrophages in AS. Pathway validation also demonstrated that the IL-17 signaling pathway was a key pathway for the differentiation of monocytes into macrophages.</p></sec><sec><title>Conclusions</title><p>The five HGs may promote the differentiation of monocytes into macrophages by influencing the IL-17 signaling pathway, leading to SLE complicated by AS. Our study provides insights into the mechanisms of SLE complicated by AS.</p></sec>