Neutrophil extracellular traps as a potential marker of systemic lupus erythematosus activity.

The heterogeneity of systemic lupus erythematosus (SLE) poses a significant challenge in identifying biomarkers for assessing disease activity. Currently, there is a paucity of established biomarkers capable of evaluating SLE flares. This study aimed to identify novel biomarkers that exhibit improved diagnostic accuracy in assessing SLE activity. A cross-sectional study was conducted at Zhongshan Hospital Xiamen University from August 2021 to April 2024,enrolling 118 patients with SLE, including 81 cases of active SLE, 50 cases of active lupus nephritis (LN) and 30 cases of active non-LN. The objective was to evaluate the diagnostic accuracy of novel biomarker called Neutrophil Extracellular Traps(NETs) for SLE activity and analyze its correlations with conventional biomarkers such as complement C3, C4, and anti-dsDNA. Serum NETs levels were significantly elevated in patients with active SLE and active LN(P < 0.001). Furthermore, positive correlations were observed between NETs levels and disease activity score based on Systemic Lupus Erythematosus Disease Activity Index-2 K (SLEDAI-2 K) (r = 0.64, P < 0.001), as well as anti-dsDNA antibody (r = 0.54, P < 0.001).Conversely, the NETs levels were negativity correlated with complement C3 concentration (r = -0.50, P < 0.001), as well as C4 concentration (r = -0.34,P < 0.001). Univariate and multivariate analysis revealed two biomarkers performed statistical significance: NETs (OR = 6.802, 95 %CI: 2.414-19.167,P < 0.001) and anti-dsDN A(OR = 3.95,95 %CI:1.582-9.864, P = 0.003). NETs had the highest AUC of 0.82(P < 0.001), with a cut-off at 515.47 ng/L demonstrating 61.63 % sensitivity and 96.87 % specificity. For the active LN group, the AUC was found to be 0.97 (P < 0.001), with a cutoff value of 515.47 ng/L, sensitivity of 100 %, and specificity of 59.76 %. Moreover, the active non-LN group had AUC of 0.70 (P = 0.007), with the same cutoff value, sensitivity of 89.61 %, and specificity of 51.61 %. In contrast to conventional laboratory markers, serum NETs represent a novel diagnostic marker for assessing disease activity in SLE, demonstrating promising potential for clinical application.

Zeng Y ，Xu W ，Chao P ，Xiao Y ，Yang T ... -  《-》

[Analysis of characteristics related to the disease activity of systemic lupus erythematosus and construction of an evaluation model].

Wang H ，Li X ，Fang K ，Zhu H ，Jia R ，Wang J ... -  《-》

Quantification of Citrullinated Histone H3 as a Marker for Neutrophil Extracellular Traps Correlated to Clinical Characteristics of Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis is not fully understood to date. One of the suggested mechanisms for its development is NETosis, which involves the release of a specific network consisting of chromatin, proteins, and enzymes from neutrophils, stimulating the immune system. One of its markers is citrullinated histone H3 (H3Cit). This study aimed to evaluate the correlation of H3Cit levels with the clinical characteristics of 80 SLE patients. Levels of H3Cit in the subjects' serum were quantified spectrophotometrically. Statistical analysis was performed using MedCalc 15.8 and Statistica 13.3. Significantly higher H3Cit levels were found in patients with arthralgia (medians [interquartile range] [IQR]: 1.67 [1.67-1.69] vs. 1.67 [1.62-1.68], p = 0.0150, respectively) and reduced complement component C4 levels compared to patients without these conditions (medians [IQR]: 1.68 [1.67-1.70] vs. 1.68 [1.67-1.69], p = 0.0297, respectively). A significant weak negative correlation was observed between H3Cit levels and leukocytosis (rho = -0.2602, p = 0.0309) and reduced complement component C3 levels (rho = -0.2442, p = 0.0447) and a weak positive correlation with anti-double stranded DNA (anti-dsDNA) antibody levels (rho = 0.3794, p = 0.0036). Moreover, the clinical utility of the H3Cit assay in differentiating patients with arthralgia (area under the curve [AUC] = 0.709, p = 0.0115), seizures (AUC = 0.813, p = 0.0005), hepatomegaly (AUC = 0.746, p = 0.0111), and reduced levels of complement component C4 (AUC = 0.662, p = 0.0224) and without the above conditions was noted.

Dubaj M ，Homa-Mlak I ，Majdan A ，Mlak R ，Majdan M ，Małecka-Massalska T ... -  《-》

Serum galectin-3 can help distinguish lupus nephritis from systemic lupus erythematosus and is also correlated with the degree of renal damage in lupus nephritis.

Lupus nephritis (LN) constitutes a substantial contributor to morbidity and mortality in systemic lupus erythematosus (SLE). The monitoring of renal function in patients with LN is associated with improved prognostication. The objective of this study was to evaluate the clinical utility of serum galectin-3 (Gal-3) levels in differentiating LN from SLE. Moreover, we sought to ascertain whether serum galectin-3 levels can serve as a marker for the degree of renal impairment in patients with LN. In this cross-sectional study, 42 patients with LN and 12 patients with SLE without nephritis were enrolled. Furthermore, 110 healthy subjects were recruited as controls. Serum Gal-3 levels were quantified using a time-resolved fluoroimmunoassay. Furthermore, Gal-3 levels were analyzed in conjunction with other clinical variables. The results demonstrated that patients with LN exhibited a significantly elevated serum Gal-3 concentration (35.98 ± 20.68 ng/mL) in comparison to healthy controls (10.11 ± 2.75 ng/mL, P < .001) and patients with SLE (14.38 ± 2.26, P < .001). The area under the curve of Gal-3 in distinguishing patients with SLE from patients with LN was 0.9157. When the cutoff value was set to 18.91 ng/mL, the sensitivity was 83.33%, and the specificity was 100%. There was a tendency for serum Gal-3 levels to increase with worsening renal impairment in patients with LN. In conclusion, Gal-3 could be a valuable biomarker for distinguishing LN from SLE, providing a useful clinical reference. Elevated serum Gal-3 levels may be associated with the severity of renal impairment in patients with LN.

Wu J ，Yu X ，Liu X ，Chen J ，Zhou X ，Zhao X ，Qin Y ，Huang B ，Chen Y ... -  《-》

The diagnostic and predictive potential of lncRNA CASC2 targeting miR-155 in systemic lupus erythematosus patients with nephritis complication.

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients' group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients' group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression.

Mohamed NR ，El-Fattah ALA ，Shaker O ，Sayed GA ... -  《Scientific Reports》