Integrated analysis of lncRNAs expression profiling in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with serious harm to human health and various clinical manifestations, which is characterized by over-activity of lymphocytes, production of autoantibodies, and effects on multiple organs.1 So far, the pathogenesis of SLE remains unclear; it is believed that genetic, environmental, infectious, and other factors participate in the pathogenesis of SLE. With the gradual in-depth study of transcriptomics, genetic factors may be the root cause of SLE,2 and epigenetics plays an important role in genetic factors of SLE.3 Epigenetics means heritable changes in gene expression without shifting the DNA sequence. The principal mechanisms of epigenetic regulation include histone modification, DNA methylation, and regulation of noncoding RNA. In the past, studies of transcriptomics mainly focused on protein-coding genes. However, protein-coding genes that encode exons account for 1.5% of the genome, and genes without protein-coding capability account for more than 80% of the human genome.4 Therefore, studies of transcriptomics began to pay attention to long noncoding RNAs (lncRNAs), which play key roles in transcription control, posttranscriptional processing, protein metabolism, immune cell differentiation, and immune responses.5 However, knowledge of related lncRNAs in SLE remains limited. The aim of our study was to investigate the levels of differential expression of lncRNAs in the peripheral blood mononuclear cells (PBMCs) of SLE patients and their correlation with disease activity, clinical features, and cell differentiation. Peripheral venous blood 4 mL was separately collected from 11 SLE patients in the active stage before treatment and stable stage after treatment, and 11 sex-and age-matched healthy individuals. PBMCs were isolated from peripheral blood samples, and total RNA was extracted from PBMCs. IlluminaPE150 was carried out to sequence, and Hisat2 was used for comparative analysis. Cuffmerge software merged the transcripts by splicing each sample and comparing them with known databases. Detailed methods and statistical analysis are shown in Supporting Information. To explore the potential functions of lncRNAs in SLE, we analyzed the expression profiles of lncRNAs. The volcano plots were used to show the overall distribution of lncRNAs between the two groups (Figure 1A,B). In this experimental data, 338 lncRNAs were differentially expressed between SLE patients and controls; 173 lncRNAs were upregulated, while 165 lncRNAs were downregulated. And 17 lncRNAs were significantly downregulated between SLE patients in the active stage before treatment and the stable stage after treatment. We further investigate the relationship of aberrantly expressed lncRNAs with clinical characteristics (SLE Disease Activity Index [SLEDAI], erythrocyte sedimentation rate, C-reactive protein expression, complement 3, complement 4, and immune cells) (Supporting Information: Tables S1–S3). Data analysis demonstrated that the expression level of CHROMR is positively correlated with SLEDAI (r = 0.435, p = 0.043). The expression level of AP001610.2 is positively correlated with SLEDAI (r = 0.506, p = 0.016) and Th2 cells (r = 0.782, p = 0.017) and is negatively correlated with C3 (r = −0.541, p = 0.017) and Treg cells (r = −0.767, p = 0.01). And the expression level of LINC01484 is positively correlated with Th2 cells (r = 0.889, p = 0.001) and is negatively correlated with Treg cells (r = −0.961, p < 0.001). In summary, the abnormal expression of lncRNAs in PBMCs of SLE patients is associated with disease activity, lymphocyte differentiation, or C-reactive protein, indicating the important role of lncRNAs in SLE pathogenesis. However, until now, the functions of most lncRNAs in SLE are still unknown, and further studies are still required to explore their roles in SLE. All authors contributed to the article, and authors Fen Zhang, Guifang Zhao, Yujie Bu, Xing Cen, Rong Zhao, Fengwu Chen, Shengxiao Zhang, and Junwei Chen have read and approved the submitted version. This study was supported by the Natural Science Research Project of Shanxi Province, Grand/Award Number 20210302123275. The authors declare no conflict of interest. This study was approved by the Ethics Committee of the Second Hospital of Shanxi Medical University (No. 2021YX147). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.