AUTHOR=Zhang Xiaojing , Zhang Jiali , Pan Zhaobing , Zhang Yuxi , Xu Xiaoqing , Sheng Yujun , Zhu Zhengwei , Zhou Fusheng , Wen Leilei 

TITLE=Transcriptome sequencing reveals novel molecular features of SLE severity

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1121359

DOI=10.3389/fgene.2023.1121359

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of autoantibodies, immune complex deposition, and tissue/organ damage. In this study, we aimed to identify molecular features and signaling pathways associated with SLE severity using RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical parameters.</p><p><bold>Methods:</bold> We analyzed transcriptome profiles of 45 SLE patients, grouped into mild (mSLE, SLEDAI ≤ 9) and severe (sSLE, SLEDAI &gt; 9) based on SLE Disease Activity Index (SLEDAI) scores. We also collected clinical data on anti-dsDNA, ANA, ESR, CRP, snRNP, AHA, and anti-Smith antibody status for each patient.</p><p><bold>Results:</bold> By comparing gene expression across groups, we identified 12 differentially expressed genes (DEGs), including 7 upregulated (CEACAM6, UCHL1, ARFGEF3, AMPH, SERPINB10, TACSTD2, and OTX1) and 5 downregulated (SORBS2, TRIM64B, SORCS3, DRAXIN, and PCDHGA10) DEGs in sSLE compared to mSLE. Furthermore, using the CIBERSORT algorithm, we found that Treg cells were significantly decreased in sSLE and negatively correlated with AMPH expression, which was mainly expressed in Treg cells from SLE patients according to public scRNA-seq data (GSE135779).</p><p><bold>Discussion:</bold> Overall, our findings shed light on the molecular mechanisms underlying SLE severity and provide insight into potential therapeutic targets.</p>