Single-cell analysis with childhood and adult systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34^-) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.

Keywords:

• Single-cell analysis
• childhood SLE
• adult SLE
• PBMC composition
• transcription

Author’ contributions

J.C. and Y.Z. conceived and designed the project; Y.L., X.Y. and J.W. analysed data; X.J. and Y.L. collected the data; Y.L., X.Y. and J.W. wrote the manuscript; and all authors revised and approved the manuscript.

Disclosure statement

The authors declare no competing interests.

Availability of data and materials

We downloaded the PBMC’ 10X scRNA-seq matrix data of 43 SLE patients (33 cSLE and 10 aSLE patients) and 18 health donors (11 cHD and 7 aHD) from Gene Expression Omnibus (GEO) database under the accession number GSE135779 and GSE142016 [14,17].

Additional information

Funding

This work was supported by the Medical Science and Technology Reserved Talent of Kunming City Health Science and Technology cultivation program of China (grant no. 2022-SW (Reserve) − 00).