Author:
Khalid R. Kreem and Ibrahim A. Altamemi
Page: 1-13
Published online: 29 Jan 2026
https://doi.org/10.36478/acerjrsb. 2026.1.13
Systemic lupus erythematosus (SLE) disease a condition as one of the causes of loss of tolerance to several autoantigens triggering the involvement of the immune system to the destruction of tissues. One of the most disabling symptoms of systemic lupus erythematosus (SLE) refers to lupus nephritis (LN). It does also have a frequency‐of‐occurrence that is dependent on some level of kidney inflammation. The immune complexes accumulated in the mesangial, subepithelial and subendothelial parts of the glomeruli cause the kidneys damage by causing several inflammatory, proliferative and fibrous pathways in these regions. The patterns of deposition of different immune complexes are associated with different lupus types of nephritis (LN) and their clinical chemistry symptoms. This research paper set out to assess the use of blood and urine cell‐free DNA (cfDNA) as a non‐invasive lupus nephritis biomarker in patients. In addition, serum microRNA‐27a and serum INF‐Y evaluated whether there were any correlations with the severity of the disease. The participants in this study were divided into three groups and the number of participants was 106. The initial group was patients who had SLE and had 6 males and 27 females (n=36). Moreover, 12 men, 24 women were patients with nephritis (n=35). Lastly, 11 men, 24 women were those who were not affected by SLE or nephritis (n=35). Three groups participated in a cross‐sectional study was conducted based on 106 participants was classified as follows: 36 patients with SLE (6 men and 27 women), 35 patients with lupus nephritis (12 men and 24 women), and 35 as a control group (11 men and 24 women) without a history of systemic disease. The study was conducted from January 2024 to September 2024. All participants had been selected from Al‐Sader Teaching Medical City in Najaf province and private labs. The study involved three groups: lupus nephritis (n=35), systemic lupus erythematosus (SLE, n=36), and healthy controls (n=35). The lupus nephritis group included 12 males and 23 females, while the SLE group had 9 males and 27 females. The healthy control group had 11 males and 24 females. Across all groups (n=106), there were 32 males and 74 females, showing a case‐control ratio of 2.03:1 for 71 diseased individuals compared to 35 healthy controls. sex distribution did not differ significantly among the groups (p=0.685). The age distribution in the study groups showed the following: lupus nephritis (n=35) had 9 under 20, 11 aged 20‐30, 9 aged 31‐40, 5 aged 41‐50, and 1 over 50. The systemic lupus erythematosus (SLE) group (n=36) included 4, 9, 14, 8, and 1 in the respective age ranges. The healthy control group (n=35) comprised 1, 6, 15, 13, and 0 individuals. In total (n=106), there were 14 participants under 20, 26 aged 20‐30, 38 aged 31‐40, 26 aged 41‐50, and 2 over 50. Statistical analysis indicated significant association between age group and group membership (p = 0.271). The levels of pro‐inflammatory cytokine INF‐T was evaluated across the three studied groups, where the median levels were significantly higher in both the lupus nephritis group (70.00, IQR = 429.00) and the SLE group (48.00, IQR = 386.75) compared to the healthy control group (0.70, IQR = 0.40), with an overall statistically significant difference between groups (p < 0.0001). The fold change of miRNA‐27b was markedly reduced in the lupus nephritis group (median = 0.00221, IQR = 0.00420) compared to both the SLE group and healthy controls, which showed nearly identical low levels (median = 0.00017, IQR = 0.00080 for both), also yielding a highly significant p‐value (p < 0.0001). Serum cell‐free DNA (cfDNA) levels between patients with lupus nephritis and SLE, expressed as fold change relative to healthy controls. In this analysis, the healthy control group showed no detectable Ct values in RT‐PCR, indicating minimal or undetectable cfDNA levels; therefore, a default fold change value of 1 was assigned to the control group for quantification purposes. The lupus nephritis group had a median cfDNA fold change of 0.353 (IQR = 0.408), while the SLE group showed a median of 0.291 (IQR = 0.000). However, the difference between the two patient groups was not statistically significant (p = 0.573). The healthy control group again showed no detectable Ct values in qPCR, indicating undetectable cfDNA levels. The lupus nephritis group had a median urine cfDNA fold change of 0.0306 (IQR = 0.073), while the SLE group showed a higher median of 0.1518 (IQR = 0.162). A statistically significant difference was observed between the two groups (p = 0.036). In Conclusion This research illustrates the potential of cell‐free DNA (cfDNA) and specific microRNAs (miRNA‐27b) as non‐invasive biomarkers for assessing lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE). The study presents evidence of increased levels of pro‐inflammatory cytokine(INF‐Y) in both SLE and LN groups when compared to healthy controls, highlighting a strong inflammatory response in these conditions. Furthermore, the expression levels of miRNA‐27b was significantly reduced in LN and SLE patients, suggesting these microRNA might serve as indicators of disease activity and severity. The investigation also assessed cfDNA levels in blood and urine samples. While serum cfDNA levels showed no significant differences between LN and SLE groups, urine cfDNA levels were notably higher in the SLE cohort compared to LN patients, indicating that urine cfDNA could be a more sensitive biomarker for distinguishing between these two groups. These findings underscore the importance of incorporating cfDNA and specific microRNA markers into the diagnostic and prognostic approaches for lupus nephritis, highlighting their relevance in non‐invasive disease monitoring. Future research should focus on larger cohort studies and the molecular roles of these biomarkers in the pathogenesis of lupus nephritis and systemic lupus erythematosus. This approach could lead to more accurate, personalized treatment strategies and improved patient outcomes.