Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, China.
Laboratory for Tumor Immunology, The First Hospital of Jilin University, Changchun, China.
Front Immunol. 2024 Feb 19;15:1303611. doi: 10.3389/fimmu.2024.1303611. eCollection 2024.
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets.
We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry.
Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells.
Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.
狼疮肾炎（LN）是系统性红斑狼疮（SLE）的一种严重表现。本研究旨在鉴定 LN 特异性基因和潜在的治疗靶点。
我们对 LN 患者的外周血单个核细胞（PBMC）进行了高通量转录组测序。健康个体和无 LN 的 SLE 患者作为对照。为了验证测序结果，我们对 5 个上调和 5 个下调基因进行了 qRT-PCR。此外，通过流式细胞术评估了 TNFRSF17 靶向药物 IBI379 对患者浆细胞和 B 细胞的作用。
与对照组和无 LN 的 SLE 组相比，LN 组分别有 1493 个和 205 个差异基因，其中 70 个基因在两组中均有表达，标记为 LN 特异性。这些 LN 特异性基因在“生物质量调节”GO 术语和细胞周期途径中显著富集。值得注意的是，包括 TNFRSF17 在内的几个基因在 LN 患者和 NZB/W 小鼠的肾脏中均过度表达。TNFRSF17 水平与 LN 患者的尿蛋白水平呈正相关，与补体 C3 和 C4 水平呈负相关。TNFRSF17 靶向药物 IBI379 可有效诱导患者浆细胞凋亡，而对 B 细胞无明显影响。
我们的研究结果表明，TNFRSF17 可作为 LN 的潜在治疗靶点。此外，IBI379 为 LN 提供了一种有前途的治疗选择。
