Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.

PLAIN LANGUAGE SUMMARY

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Furthermore, SLE women have an increased likelihood of encountering adverse pregnancy outcomes such as diabetes and hypertension. The etiology of SLE involves a multifaceted interplay of genetic, immune, endocrine, and environmental factors, which contributes to a breakdown in the immune system’s tolerance to self-antigens. Recent studies have highlighted a strong correlation between the severity of renal involvement in lupus nephritis and B cell dysfunction in patients, as elucidated through single-cell transcriptomics. Additionally, comparative studies have revealed notable differences in the immune cell profile between pregnant women with lupus and healthy pregnant women. A key observation the marked reduction in the proportion of CD4+ T cells in pregnant women suffering from lupus. Despite these findings, the detailed transcriptomic alterations within high-resolution immune cell profiling during activate phase of SLE in pregnancy remain inadequately understood. In our study, we focused on comparing the transcriptomic expression patterns of peripheral blood immune cells between pregnant women with active SLE and those with stable SLE. Our data confirmed significant differences in IFN signaling and pregnancy-related factors in T cells, NK cells, B cells, and macrophages, contrasting the immune cells of pregnant women with active SLE against those with stable SLE. Additionally, the proportion of CD56+ NK cells was significantly increased in pregnant women with SLE. The correlation between the transcriptomic profiles of immune cells and the activity of SLE during pregnancy may provide potential strategies for predicting and treating SLE during pregnancy.

Graphical Abstract

Keywords:

• Systemic lupus erythematosus
• single-cell sequence
• pregnant

Author contributions

Conceptualization: Yuezhen Li and Juntao Liu. Data curation: Yijun Song, Jiuliang Zhao, and Mengtao Li. Formal analysis: Congcong Liu, Zeyang Yu and Xiaojie Zhang. Methodology: Congcong Liu. Project administration: Yuezhen Li and Juntao Liu. Resources: Congcong Liu, Zeyang Yu, Yijun Song, Xiaojie Zhang, Jiuliang Zhao, and Mengtao Li. Software: Zeyang Yu, and Qian Yu. Supervision: Yuezhen Li. Validation: Qian Yu. Visualization: Juntao Liu. Writing of the original draft: Congcong Liu, Zeyang Yu, and Yijun Song. Writing, review & editing: Yuezhen Li and Juntao Liu.

Disclosure statement

Z.Y., X.Z., Q.Y., and Y.L. are Berry Genomics employees. The other authors declare that the research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest.

Data availability statement

The raw sequence data presented in this manuscript have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2021) in National Genomics Data Center (Nucleic Acids Res 2022), China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA-Human: PRJCA014813), and are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human. Temporary links can be found at https://ngdc.cncb.ac.cn/search/. The script has been made available on GitHub at the following link: https://github.com/yuzeyangisci/sc_SLE-script/.

Additional information

Funding

This work received support from the Beijing Municipal Natural Science Foundation (No. 7212072), Beijing Municipal Science & Technology Commission (No. Z201100005520022,23, 25-27), CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-B-013, C-002, D-009).