Objective Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects. Methods We performed RNA sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n = 4), SLE (n = 5) and control (n = 3) individuals, differential gene expression analysis (DGEA) and enrichment analysis using gene ontology (GO) and CORUM, KEGG and Reactome pathway databases. Results Two-dimensional projection showed a distinct gene profile in primary APS vs control kidneys samples, but similar to SLE. DGEA in APS vs controls returned 276 upregulated and 217 downregulated genes, while the comparison between APS and SLE identified 75 upregulated and 111 downregulated genes. In 276 upregulated genes, enriched GO terms were (innate) immune response, inflammatory response, leucocyte and lymphocyte activation, cytokine production and T cell activation. CORUM and KEGG revealed complement-related genes (C3, C4A, C4B). Expression levels showed logFC values of 2.25 (P = 1.58e-05) for C3, 2.17 (P = 2.69e-06) for C4A and 2.135 (P = 3.7e-06) for C4B in APS vs controls, without differences between APS and SLE. Interferon (IFN) alpha/beta signalling was revealed by Reactome. Expression levels of nine IFN-regulated genes found upregulated in APS vs control kidneys (P-values ≤ 0.001 for all). Examining neutrophil-extracellular traps (NETs)-related gene expression, 13 of 15 upregulated NETs-related genes exhibited higher expression in APS vs controls but not vs SLE. Conclusion Complement, interferon and NETs-related genes are highly expressed in APS kidney tissues, similarly to SLE, pointing out the role of innate immunity in APS nephropathy pathogenesis and potential treatment targets.

中文翻译：

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原发性抗磷脂综合征的肾脏全转录组分析揭示了补体、干扰素和 NETs 相关基因表达


目的 抗磷脂综合征（APS）的发病机制仍不清楚。我们的目的是首次评估原发性 APS 与系统性红斑狼疮 (SLE) 和对照受试者的肾脏转录组谱。方法 我们对来自 APS (n = 4)、SLE (n = 5) 和对照 (n = 3) 个体的档案福尔马林固定石蜡包埋的肾活检进行 RNA 测序、差异基因表达分析 (DGEA) 和使用基因的富集分析本体论 (GO) 以及 CORUM、KEGG 和 Reactome 途径数据库。结果二维投影显示原发性 APS 与对照肾脏样本中的基因谱不同，但与 SLE 相似。 APS 与对照中的 DGEA 返回了 276 个上调基因和 217 个下调基因，而 APS 和 SLE 之间的比较发现了 75 个上调基因和 111 个下调基因。在 276 个上调基因中，丰富的 GO 术语是（先天）免疫反应、炎症反应、白细胞和淋巴细胞激活、细胞因子产生和 T 细胞激活。 CORUM 和 KEGG 揭示了补体相关基因（C3、C4A、C4B）。表达水平显示，在 APS 与对照中，C3 的 logFC 值为 2.25 (P = 1.58e-05)，C4A 的 logFC 值为 2.17 (P = 2.69e-06)，C4B 的 logFC 值为 2.135 (P = 3.7e-06)，APS 之间没有差异和系统性红斑狼疮。 Reactome 揭示了干扰素 (IFN) α/β 信号传导。与对照肾脏相比，APS 肾脏中九个 IFN 调节基因的表达水平上调（所有 P 值均≤ 0.001）。检查中性粒细胞胞外陷阱 (NET) 相关基因表达，15 个上调的 NETs 相关基因中有 13 个在 APS 中与对照相比表现出更高的表达，但与 SLE 相比则没有。 结论 补体、干扰素和NETs相关基因在APS肾组织中高表达，与SLE相似，指出先天免疫在APS肾病发病机制中的作用和潜在的治疗靶点。