Scholarlink

<p>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and multi-organ involvement due to dysregulated immune responses. Ongoing research aims to understand the underlying mechanisms of this immune dysregulation, with particular interest in immune checkpoint molecules such as VISTA (encoded by the <i>VSIR</i> gene), which exerts context-dependent immunomodulatory effects. We analyzed a large-scale single-cell RNA-seq (scRNA-seq) dataset (GSE174188) comprising 261 samples (162 SLE cases, 99 controls) to investigate <i>VSIR</i> expression patterns across peripheral blood mononuclear cell (PBMC) subsets in SLE versus controls, using bioinformatics tools. Additionally, fresh PBMCs were isolated from SLE patients and healthy controls, and <i>VSIR</i> mRNA levels were quantified by RT-qPCR in treatment-naïve cases and those receiving Prednisolone, Hydroxychloroquine, or supplementary medications. Associations between <i>VSIR</i> expression and clinical/demographic parameters, including disease activity index, were also evaluated. scRNA-seq analysis revealed significantly upregulated <i>VSIR</i> expression in monocytes from SLE patients compared to healthy controls. In contrast, pseudobulk differential expression analysis of the entire PBMC population, corroborated by RT-qPCR on fresh samples, demonstrated downregulation of <i>VSIR</i> in SLE cases overall (log₂ fold change = -1.23). Notably, <i>VSIR</i> expression differed across treatment groups, with the lowest levels observed in treatment-naïve patients and higher levels in those receiving first-line therapies (prednisolone and hydroxychloroquine). Furthermore, <i>VSIR</i> expression exhibited a significant negative correlation with SLE disease activity index. This study demonstrates decreased <i>VSIR</i> expression in the whole PBMC population in SLE patients, suggesting a potential role in disease pathogenesis processes possibly through altered immune checkpoint regulation. Moreover, <i>VSIR</i> expression was associated with treatment status, with higher expression observed in patients receiving standard first-line therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Expression of VISTA on peripheral blood mononuclear cells in Systemic lupus erythematosus: association with disease activity and treatment status

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

查看全文
  • Afsaneh Enteshari-Moghaddam,
  • Rozita Abolhasan,
  • Meysam Motevasseli,
  • Nasrin Fouladi,
  • Majid Eterafi,
  • Sahar Samemaleki,
  • Hamed Kyanfar,
  • Elham Safarzadeh

摘要

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and multi-organ involvement due to dysregulated immune responses. Ongoing research aims to understand the underlying mechanisms of this immune dysregulation, with particular interest in immune checkpoint molecules such as VISTA (encoded by the VSIR gene), which exerts context-dependent immunomodulatory effects. We analyzed a large-scale single-cell RNA-seq (scRNA-seq) dataset (GSE174188) comprising 261 samples (162 SLE cases, 99 controls) to investigate VSIR expression patterns across peripheral blood mononuclear cell (PBMC) subsets in SLE versus controls, using bioinformatics tools. Additionally, fresh PBMCs were isolated from SLE patients and healthy controls, and VSIR mRNA levels were quantified by RT-qPCR in treatment-naïve cases and those receiving Prednisolone, Hydroxychloroquine, or supplementary medications. Associations between VSIR expression and clinical/demographic parameters, including disease activity index, were also evaluated. scRNA-seq analysis revealed significantly upregulated VSIR expression in monocytes from SLE patients compared to healthy controls. In contrast, pseudobulk differential expression analysis of the entire PBMC population, corroborated by RT-qPCR on fresh samples, demonstrated downregulation of VSIR in SLE cases overall (log₂ fold change = -1.23). Notably, VSIR expression differed across treatment groups, with the lowest levels observed in treatment-naïve patients and higher levels in those receiving first-line therapies (prednisolone and hydroxychloroquine). Furthermore, VSIR expression exhibited a significant negative correlation with SLE disease activity index. This study demonstrates decreased VSIR expression in the whole PBMC population in SLE patients, suggesting a potential role in disease pathogenesis processes possibly through altered immune checkpoint regulation. Moreover, VSIR expression was associated with treatment status, with higher expression observed in patients receiving standard first-line therapies.