Determining IFI44 as a key lupus nephritis’s biomarker through bioinformatics and immunohistochemistry

Lupus nephritis (LN) emerges as a severe complication of systemic lupus erythematosus (SLE), significantly affecting patient survival. Despite improvements in treatment reducing LN’s morbidity and mortality, existing therapies remain suboptimal, emphasizing the necessity for early detection to improve patient outcomes. This study employs bioinformatics and machine learning to identify and validate potential LN biomarkers using immunohistochemistry (IHC). It explores the relationship between these biomarkers and the clinical and pathological characteristics of LN, assessing their prognostic significance. The research provides deeper mechanistic insights by employing Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the study characterizes the immune profiles of LN patients through the CIBERSORT algorithm, focusing on the role of interferon-inducible protein 44 (IFI44) as a key biomarker. IFI44 shows elevated expression in LN-affected kidneys, compared to healthy controls. The levels of IFI44 positively correlate with serum creatinine and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and inversely with serum complement C3 and initial estimated glomerular filtration rate (eGFR). IFI44 is identified as a promising biomarker for LN, offering potential to refine the assessment of disease progression and predict clinical outcomes. This facilitates the development of more personalized treatment strategies for LN patients.

狼疮性肾炎（Lupus nephritis, LN）是系统性红斑狼疮（systemic lupus erythematosus, SLE）的严重并发症之一，可显著影响患者生存预后。尽管当前治疗手段的进步已降低了LN的发病率与死亡率，但现有疗法仍未达最优，凸显了早期检测对改善患者转归的必要性。本研究借助生物信息学与机器学习方法，利用免疫组化（immunohistochemistry, IHC）技术筛选并验证潜在的LN生物标志物，探究这些标志物与LN临床及病理特征的关联，并评估其预后价值。研究通过基因集富集分析（Gene Set Enrichment Analysis, GSEA）、基因本体（Gene Ontology, GO）及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析，进一步揭示了LN的潜在分子机制。此外，本研究通过CIBERSORT算法刻画了LN患者的免疫微环境特征，并重点聚焦于干扰素诱导蛋白44（interferon-inducible protein 44, IFI44）作为关键生物标志物的作用。研究发现，与健康对照相比，IFI44在受累肾脏组织中呈高表达；其表达水平与血清肌酐、系统性红斑狼疮疾病活动指数（Systemic Lupus Erythematosus Disease Activity Index, SLEDAI）呈正相关，与血清补体C3、初始估算肾小球滤过率（estimated glomerular filtration rate, eGFR）呈负相关。综上，IFI44被鉴定为极具潜力的LN生物标志物，可为精准评估疾病进展、预测临床转归提供依据，进而助力LN患者个体化治疗策略的优化与开发。