A recent study published in Human Molecular Genetics has spotlighted E74-like factor 1 (ELF1) as a potential biomarker for disease activity and renal involvement in systemic lupus erythematosus (SLE). This autoimmune disease, known for its multi-organ impact and complex pathogenesis, has long lacked precise biomarkers to guide diagnosis and management. The study combined advanced genomic tools, including Mendelian randomization and HEIDI analysis, to investigate data from large-scale Genome-Wide Association Studies (GWAS) and expression Quantitative Trait Loci (eQTL).
Seven novel functional genes were identified as being associated with SLE, with ELF1 emerging as a significant focus. In patients with SLE, ELF1 expression levels were notably reduced in CD4+ T cells compared to healthy controls. Further subgroup analysis revealed a consistent decrease in ELF1 expression in individuals presenting with key disease characteristics, such as low serum complement C3 levels, proteinuria, new-onset skin rashes, and high SLE Disease Activity Index (SLEDAI) scores. Analysis of receiver operating characteristic (ROC) curves demonstrated its high accuracy in distinguishing SLE cases (AUC = 0.9493) and in assessing disease activity (AUC = 0.6852) and renal involvement (AUC = 0.7363). These findings suggest that ELF1 could serve as a reliable marker not only for diagnosing SLE but also for monitoring disease progression and organ-specific involvement.
ELF1 is part of the ETS family of transcription factors that oversee the expression of numerous genes and are crucial for processes like hematopoiesis, as well as the development and function of immune cells and angiogenesis. It functions as both an enhancer and a repressor to modulate gene transcription. A genetic study conducted with 3,300 Asian patients with SLE and 4,200 controls identified ETS1 (rs1128334) as a significant risk factor for the disease. ETS1 is a vital transcription factor involved in immune functions, including Th17 cell development and B lymphocyte differentiation, and it exhibited decreased expression linked to the risk allele. This finding underscores the important role of ETS1 in the pathogenesis of SLE, shedding light on its influence on immune dysregulation and the underlying mechanisms of the disease. Another genetic study involving 3,164 SLE patients and 4,482 controls across Asian populations identified ELF1 (rs7329174) as significantly associated with systemic lupus erythematosus (OR = 1.26, P = 1.47 × 10⁻⁸). While no direct link between rs7329174 and ELF1 transcript variants was observed, the study highlights the gene’s importance in SLE susceptibility and suggests its expression is tightly regulated.
This is the first study to report the significant reduction of ELF1 expression in SLE patients, underscoring its role as a susceptibility gene and its relevance to disease phenotype and activity. The research provides crucial insights into SLE pathogenesis and lays the groundwork for further exploration into the regulatory mechanisms of ELF1. Such advancements could ultimately drive the development of targeted therapies, offering hope for more precise and effective treatment options in SLE management.
References
- Zhang Y, Cai M, Huang X, Zhang L, Wen L, Zhu Z, Gao J, Sheng Y. ELF1 serves as a potential biomarker for the disease activity and renal involvement in systemic lupus erythematosus. Sci Rep. 2024 Nov 4;14(1):26590.
- Yang J, Yang W, Hirankarn N, Ye DQ, Zhang Y, Pan HF, et al. ELF1 is associated with systemic lupus erythematosus in Asian populations. Hum Mol Genet. 2011 Feb 1;20(3):601-7.
- Yang W, Shen N, Ye DQ, Liu Q, Zhang Y, Qian XX, Hirankarn N, Ying D, Pan HF, Mok CC, Chan TM, Wong RW, Lee KW, Mok MY, Wong SN, Leung AM, Li XP, Avihingsanon Y, Wong CM, Lee TL, Ho MH, Lee PP, Chang YK, Li PH, Li RJ, Zhang L, Wong WH, Ng IO, Lau CS, Sham PC, Lau YL; Asian Lupus Genetics Consortium. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet. 2010 Feb 12;6(2):e1000841.