Systemic Lupus Erythematosus Levels Research Articles

Uncoupling interferons and the interferon signature explains clinical and transcriptional subsets in SLE

Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature. Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. Here, we show that IFN type levels in SLE vary significantly across clinical and transcriptional endotypes. Whereas skin involvement correlated with IFN-I alone, systemic features like nephritis associated with co-elevation of IFN-I, IFN-II, and IFN-III, indicating additive IFN effects in severe SLE. Notably, while high IFN-II/-III levels without IFN-I had a limited effect on disease activity, IFN-II was linked to IFN-I-independent transcriptional profiles (e.g., OXPHOS and CD8+GZMH+ cells), and IFN-III enhanced IFN-induced gene expression when co-elevated with IFN-I. Moreover, dysregulated IFNs do not explain the IFN signature in 64% of patients or clinical manifestations including cytopenia, serositis, and anti-phospholipid syndrome, implying IFN-independent endotypes in SLE. This study sheds light on mechanisms underlying SLE heterogeneity and the variable response to IFN-targeted therapies in clinical trials.

Duplex Vertical-Flow Rapid Tests for Point-of-Care Detection of Anti-dsDNA and Anti-Nuclear Autoantibodies.

The goal of this study is to develop a rapid diagnostic test for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HCs). Observer scores and absolute signal intensities from the VFA were validated via ELISA. The rapid point-of-care VFA test that was engineered demonstrated a limit of detection of 0.5 IU/mL for ANA and αDNA autoantibodies in human plasma with an inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in SLE and HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and an 84% ROC AUC value in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease, and rapid turnaround, it can also be used to assess SLE prevalence estimates.

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway.

Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of β-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG's impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.

Plasma/Serum Oxidant Parameters in Systemic Lupus Erythematosus Patients: A Systematic Review and Meta-Analysis.

Most published results have revealed variations in the association of serum/plasma levels of malondialdehyde (MDA), apolipoprotein B (ApoB), and oxidized low-density lipoprotein (OxLDL) and systemic lupus erythematosus (SLE). This study was performed to establish MDA, ApoB, and OxLDL levels in systemic lupus erythematosus (SLE) patients. Electronic databases were searched for the included articles up to 27th February 2023. The meta-analysis included 48 articles with 2358 SLE patients and 2126 healthy controls considered for MDA, ApoB, and OxLDL levels. There were significantly higher MDA, ApoB, and OxLDL levels in SLE patients than those in the control groups. Subgroup analysis indicated that European/American SLE patients and patients of both ages <36 and ≥36 exhibited higher MDA, ApoB, and OxLDL levels. Arab and Asian SLE patients had higher ApoB and MDA/OxLDL levels. African SLE patients recorded higher OxLDL levels than the control groups. SLE patients with a body mass index (BMI) of ≥23 and a disease duration of <10 recorded significantly higher MDA, ApoB, and OxLDL levels. Patients with systemic lupus erythematosus disease activity index (SLEDAI) ≥8 of SLE had higher MDA and ApoB levels, whereas SLE patients with SLEDAI <8 showed significantly higher ApoB levels. Patients with BMI <23 of SLE had higher MDA and OxLDL levels. This study established significantly higher MDA, ApoB, and OxLDL levels in SLE patients, suggesting a possible role of MDA, ApoB, and OxLDL in the disease.

Effectiveness in the Long-Term Follow-Up of Brief Group Psychoanalytic Psychotherapy in Quality of Life, Symptoms, Coping, Anxiety, and Depression in Systemic Lupus Erythematosus Patients

Objective: To evaluate the effectiveness in the long-term follow-up of brief group psychoanalytic psychotherapy in improving quality of life, symptoms, coping strategies, anxiety, and depression levels in systemic lupus erythematosus (SLE) patients. Methods: Prospective, randomized clinical trial including 80 SLE patients divided into two groups: therapy (n=37) and control (n=43), with standard clinical care. Therapy group received weekly therapy for 20 weeks. The assessments were at baseline, after 20 weeks and after 24 months from the end of intervention. Damage and disease activity were assessed by rheumatologists. Self-administered questionnaires were supervised by blind evaluators: quality of life, symptoms, coping strategies, anxiety, and depression. Intent to treat statistical analysis. Comparisons of variance between groups over time (ANOVA repeated measures). P &lt;0.05 significant. Results: At baseline, both groups were homogeneous. After intervention, therapy group showed significant improvement in most domains of quality of life, symptoms, all domains of anxiety, and depression and several domains of coping strategies. Benefits in quality of life and coping remained at 24 months follow-up. However, the improvement in anxiety, and depression was not maintained. Medications and clinical variables did not change. Conclusion: This study showed the effectiveness of brief group psychoanalytic psychotherapy in improving quality of life, symptoms and coping strategies in SLE patients even in the long-term follow-up. Depression and anxiety levels reduced at the end of therapy, although, the improvement did not last 24 months.

Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BackgroundAn increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.MethodsRepeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.ResultsWomen with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.ConclusionOur results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.

Serum salusin-β levels in patients with systemic lupus erythematosus.

Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1pg/ml and 157.7 ± 88.7pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis.

Association of Circulating Levels of Hypoxia-Inducible Factor-1α and miR-210 with Photosensitivity in Systemic Lupus Erythematosus Patients.

miR-210, a key hypoxamiR, regulates hypoxia and inflammation-linked hypoxia. Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is responsible for many pathological disorders, including photosensitivity. This study aimed to find the correlation between circulating miR-210/HIF-1α levels and photosensitivity in SLE patients and other SLE-associated pathological complications in a single-center case-control study. The study population comprised 104 SLE Egyptian patients with photosensitivity, 32 SLE patients without photosensitivity, and 32 healthy subjects. SLE activity was assessed for all patients using the SLE Disease Activity Index (SLEDAI). Clinical complications/manifestations and hematological/serological analyses were recorded. HIF-α concentration was investigated by ELISA, and miR-210 expression was analyzed by qRT-PCR. The results revealed that circulating miR-210 was significantly increased in the SLE/photosensitivity group versus the SLE and control groups. The additional occurrence of malar rash, oral ulcers, renal disorders, or hypertension resulted in a higher expression of miR-210. SLEDAI activity status showed no effect on miR-210. Erythrocyte sedimentation rate, white blood cells, hemoglobin, platelets, patient age, and disease duration were positively correlated with circulatory miR-210. HIF-α concentration was significantly induced in the SLE/photosensitivity group versus the SLE and control groups. In SLE/photosensitivity, the presence of renal disorders and hypertension resulted in the highest HIF-α concentrations. A strong positive correlation was recorded between HIF-α concentration and circulatory miR-210 in SLE/photosensitivity patients (r = 0.886). The dysregulation of circulating miR-210/HIF-1α levels in SLE/ photosensitivity patients is controlled by the presence of additional pathological complications, and results suggest that the hypoxia pathway might interact positively with the pathogenesis and disease progression of SLE.

Expression pattern of glucocorticoid receptor α gene and associations with clinicolaboratory features in patients with systemic lupus erythematosus.

Glucocorticoid receptor α (GRα) gene is a transcription factor with clinically significant immune-modulating properties in various autoimmune diseases. However, the expression pattern of the GRα gene and associations with clinical features in patients with systemic lupus erythematosus (SLE) is controversial. This study aimed to assess the correlation between the GRα expression and different clinical and laboratory-related parameters in SLE patients. A total of 45 women with newly diagnosed SLE and 31 gender and age-matched healthy controls were enrolled in this cross-sectional study. The real-time quantitative PCR (qRT-PCT) method evaluated the differences in GRα expression in peripheral blood mononuclear cells from cases and controls. The correlation between the GRα gene expression levels, clinicolaboratory features, and potential prognostic application was also analyzed. Compared to the healthy individuals, the GRα gene expression in newly diagnosed SLE patients who did not receive any treatment was numerically reduced, but this reduction did not achieve statistical significance (P=0.87). No significant correlation was also found with the activity and severity of SLE according to SLEDAI2K (P=0.41). The GRα gene expression showed a negative correlation with CRP (P=0.034) and a positive correlation with lupus anticoagulant (P=0.039) levels in SLE. The receiver operating characteristic (ROC) curve analysis indicated that the GRα expression level might be a predictor biomarker for low CRP and positive lupus anticoagulant in SLE, respectively. This study proposed that expression of the GRα in newly diagnosed lupus patients has no statistically significant difference with healthy age and sex-matched controls. Besides, its expression does not correlate with lupus disease activity according to SLEDAI2k. However, further studies in this area are required.

Relationship between neutrophil gelatinase-associated lipocalin levels and disease parameters including clinicopathological parameters and various cytokine levels in systemic lupus erythematosus.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury and indicates tubular damage. Lupus nephritis-associated renal injury is characterized by damage to the glomeruli and tubular portions of the kidneys. Therefore, NGAL concentrations are expected to vary according to the severity of systemic lupus erythematosus (SLE). In this study, samples from (NZB × NZW) F1 mice at an advanced stage of SLE were used to determine whether serum and urine NGAL concentrations or the urine NGAL:creatinine (uNGAL/C) ratio can be used to reflect diet, disease state, and treatment efficacy. Additionally, the relationship between the levels of NGAL and various cytokines in the serum in SLE was evaluated. Mice were divided into the following four groups (n=15): CN, chow diet and no treatment (saline; intraperitonially injected [i.p.]; 200 μL/day); CP, chow diet and methylprednisolone (i.p.; 5 mg/kg/day); HN, high-fat diet and no treatment (saline [i.p.]; 200 μL/day); and HP, high-fat diet and methylprednisolone treatment (i.p.; 5 mg/kg/day) every day from 6 to 42 weeks of age. The serum and urine NGAL levels and uNGAL/C values were significantly lower in the CP group than those in the CN group. Further, serum NGAL concentration demonstrated a strong positive correlation with urine NGAL levels, uNGAL/C, urine protein concentrations, urine protein:creatinine ratio, and the expression of several cytokines associated with SLE pathogenesis (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and interferon-induced protein [IP]-10). These results suggest that NGAL has a strong positive correlation with the clinicopathological parameters and several key cytokines in SLE.

High serum immunoglobulin D levels in systemic lupus erythematosus: more to be found?

Many studies have shown that serum immunoglobulin D (IgD) is usually increased in autoimmune diseases. The potential role of IgD in systemic lupus erythematosus (SLE) is still unclear. Our study aimed to compare the serum IgD levels of SLE with different population and to evaluate the relationship between serum IgD and SLE. Fifty SLE patients, 40 non-SLE chronic kidney disease (CKD) patients, and 50 healthy volunteers were enrolled in this study. Serum IgD levels were analyzed by ELISA assay and compared between groups. The correlationof serum IgD and SLE disease were evaluated. The ability of serum IgD to predict SLE was analyzed by graphing receiver operating characteristic curves. Serum IgD levels were significantly higher in SLE patients compared to non-SLE CKD and healthy controls (7436.1 ± 5862.1 vs. 4517.8 ± 5255.2 vs. 4180.4 ± 4881ng/mL, p = 0.01, p = 0.002, respectively), and in patients with high SLE Disease Activity Index (SLEDAI) scores compared with those with low scores (8572.9 ± 5968.7 vs. 5020.4 ± 4972.5ng/mL, p = 0.044). High level of inflammatory cytokines and decreased circulating basophil counts were found in SLE patients (p < 0.05). No correlations was identified between serum IgD levels and SLEDAI scores (p > 0.05). Serum IgD was noninferior to IgG or IgE in discriminating SLE with an area under the curve of 0.672 (95% CI, 0.59-0.75). Serum IgD levels are significantly elevated in SLE patients with high SLEDAI scores. Simultaneous occurrence of increased inflammatory cytokines and decreased basophil counts highlights the potential role of IgD-targets interaction in SLE pathogenesis. Key points • Total serum IgD levels were elevated in SLE patients. • High IgD levels were significantly higher in SLE patients with high SLEDAI scores. • The ability of serum IgD was equivalent to IgG or IgE in discriminating SLE from CKD and healthy adult.

Deficiency of p53 Causes the Inadequate Expression of miR-1246 in B Cells of Systemic Lupus Erythematosus.

Underexpression of p53 is considered the leading cause of the decreased miR-1246 expression in B cells of systemic lupus erythematosus (SLE) patients, yet the exact mechanism of action still remains unclear. To further explore the molecular mechanism of p53 upregulating miR-1246 expression, we targeted the methylation and acetylation of histone H3 in the miR-1246 promoter region of SLE B cells. We found that increased histone H3 trimethylation at Lys27 (H3K27me3) and decreased histone H3 acetylation at Lys9 and Lys14 (H3K9/K14ac) in the miR-1246 promoter region are essential for the low expression of miR-1246 in SLE B cells. p53 can promote miR-1246 transcription by recruiting Jumonji domain-containing protein 3 (JMJD3), E1A-binding protein p300 (EP300), and CREB-binding protein (CBP) to bind to the miR-1246 promoter, downregulating H3K27me3 and upregulating H3K9/K14ac. Furthermore, early B cell factor 1 (EBF1), CD40, CD38, and X box binding protein-1 (XBP-1) expression levels in SLE B cells transfected with p53 expression plasmid were significantly decreased, whereas autoantibody IgG production in autologous CD4+ T cells cocultured with overexpressed p53 SLE B cells was reduced. Collectively, our data suggest that the reduction of p53 decreases miR-1246 expression via upregulation of H3K27me3 and downregulation of H3K9/14ac, which in turn results in SLE B cell hyperactivity.

Clinical significance of interleukin-36 alpha and gamma in systemic lupus erythematosus patients: Potential relation to disease activity and subclinical arthritis

Aim of the workTo assess serum of interleukin-36 alpha (IL-36α) and interleukin-36 gamma (IL-36γ) levels in systemic lupus erythematosus (SLE) patients and to explore their association with clinical and laboratory features of SLE and with ultrasound evidence of subclinical hand arthritis. Patients and methodsThe study included 84 SLE patients without overt arthritis and 84 matched controls. The serum levels of IL-36α and IL-36γ were measured and compared between patients and controls. The hands and wrists of all patients underwent musculoskeletal ultrasound evaluation for evidence of subclinical arthritis and tenosynovitis. The SLE disease activity score was assessed for all patients. ResultsThe mean of serum IL-36α (65.5 ± 38.9 pg/ml) and IL-36γ (468.9 ± 315.9 pg/ml) were significantly higher in SLE patients compared to controls (37.9 ± 17.2 pg/ml and 151.1 ± 73.4 pg/ml; p < 0.001 each). IL-36α and IL-36γ had the ability to discriminate between SLE patients and controls with an AUC of 0.69 and 0.83 respectively. Serum IL-36α was significantly correlated with SLEDAI score (p = 0.04), synovitis (p < 0.001),Us erosion score (p = 0.01) and PD signals score (p = 0.002). Serum IL-36γ was significantly correlated with serum creatinine level (p = 0.04). SLE patients with arthralgia had significantly higher IL-36α serum level than patients without (p = 0.04). SLE patients with proteinuria had significantly higher IL-36γ than those without (p = 0.04). The linear regression analysis model revealed that the US evidence of synovitis was the strongest factor associated with the serum level of IL-36α meanwhile proteinuria was the strongest factor associated with the serum level of IL-36γ. ConclusionIL-36αserum level was significantly associated with SLEDAI score, arthralgia and US evidence of subclinical arthritis. IL-36γ serum level was significantly associated with proteinuria.

LncRNA X‐inactive‐specific transcript is a potential biomarker related to changes in CD4+ T cell levels in systemic lupus erythematosus

AbstractBackgroundSystemic lupus erythematosus (SLE) is a particularly heterogeneous autoimmune disease. This study was intended to clarify the correlations between X‐inactive‐specific transcript (XIST) expression and SLE clinical features and the contribution of XIST to SLE pathogenesis at the transcriptome level.MethodsXIST expression in 79 SLE patients, 14 rheumatoid arthritis patients, and 23 healthy controls was determined by quantitative polymerase chain reaction. The Benjamini and Hochberg adjusted method and multivariate linear regression were applied to correct p‐values and adjust confounding factors, respectively. Bioinformatic methods were used to explore the function and regulatory mechanism of XIST.ResultsXIST was significantly elevated in peripheral blood mononuclear cells and CD4+ T cells from SLE patients compared with the levels in healthy controls and had potential diagnostic value for SLE. Notably, XIST expression was positively correlated with the SLE disease activity index and significantly reduced after effective treatment. Moreover, SLE patients with high XIST expression tended to have elevated levels of CD4+ T cells, but reduced levels of NK cells. Bioinformatic analyses suggested that XIST may regulate OLFM4 and CEACAM8 expression by acting as a spongy body for miR‐20a, miR‐92a, miR‐106a, and miR‐449a. Furthermore, CEACAM8 was significantly upregulated in CD4+ T cells from SLE patients and significantly positively correlated with XIST expression.ConclusionslncRNA XIST, a potential diagnostic and therapeutic biomarker for SLE, is involved in the change of immune cell balance in the peripheral blood of SLE patients. Mechanistically, XIST may regulate the miR‐17‐92–CEACAM8 axis to achieve this in CD4+ T cells.

Increased levels of sirtuin-1 in systemic lupus erythematosus.

We investigated plasma sirtuin-1 (SIRT1) levels in systemic lupus erythematosus (SLE) patients, and discussed potential of plasma SIRT1 as a biomarker for SLE. A total of 359 subjects, including 299 patients (89 SLE, 50 rheumatoid arthritis, 30 osteoarthritis, 30 gout, 38 Sjögren's syndrome, 20 ankylosing spondylitis, 30 mixed connective tissue disease, 12 systemic sclerosis) and 60 healthy controls were recruited. SIRT1 in plasma of SLE patients was detected by enzyme-linked immunosorbent assay. Relationship between SIRT1 levels, clinical, laboratory characteristics in SLE patients was discussed. Plasma SIRT1 to discriminate SLE from different rheumatic patients and healthy controls was assessed by receiver operating characteristic (ROC) curve analysis. SIRT1 levels were elevated in SLE patients compared with healthy controls (6.28 [5.89-6.68] vs 2.42 [2.10-2.74] ng/mL, P < .001). SIRT1 concentration in plasma was significantly associated with disease activity (rs =.317, P < .001). Area under the ROC curve (AUC) analysis showed that compared to healthy controls, SIRT1 had a good ability for diagnosis of SLE (AUC=0.986, P < .001). Compared with rheumatoid arthritis, osteoarthritis, Sjögren's syndrome, ankylosing spondylitis, mixed connective tissue disease and systemic sclerosis patients, the AUC of plasma SIRT1 in SLE patients was 0.982, 0.881, 0.810, 0.860, 0.781, 0.889, 0.736, respectively. When evaluating the discriminative power of SIRT1, the sensitivity and specificity for distinguishing SLE from non-SLE patients were 95.51%, 61.43%, respectively, at the optimal cut-off value of 4.323 ng/mL. Circulating SIRT1 was elevated in SLE, and might be a promising SLE diagnostic marker.

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios.

IntroductionThere is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN.MethodsThis was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment.ResultsMCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66–0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone.ConclusionMCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

Anti-RNP antibodies are associated with the interferon gene signature but not decreased complement levels in SLE

ObjectivesThe goals of these studies were to elucidate the inter-relationships of specific anti-nuclear antibody (ANA), complement, and the interferon gene signature (IGS) in the pathogenesis of systemic lupus erythematosus (SLE).MethodsData...

Elevated Circulating Thrombomodulin Levels in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Thrombomodulin (TM) is closely related to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). However, current evidence on circulating TM levels in SLE patients is contradictory. We conducted this meta-analysis to more accurately assess circulating TM levels in patients with SLE and lupus nephritis (LN) and to analyze related influencing factors. Systematic search of relevant documents was conducted in PubMed, Embase, and The Cochrane Library databases (up to 28 February 2021). Studies on the comparison of circulating TM between SLE patients and controls were screened and evaluated for inclusion. Random-effects model analysis was applied to calculate the combined standardized mean difference (SMD) with a 95% confidence interval (CI). Heterogeneity was estimated by Q statistics and I2. A total of 353 articles were identified, 14 provided adequate information for this study finally. The results illustrated that SLE patients had higher TM levels than healthy controls (SMD=0.38, 95% CI: 0.02 to 0.74, p=0.04). Circulating TM levels were increased in patients with active SLE compared to inactive SLE patients (SMD=1.12, 95% CI: 0.03 to 2.20, p=0.04). In addition, circulating TM levels of SLE patients with LN were higher than those without LN (SMD=4.55, 95% CI: 1.97 to 7.12, p=0.001). The circulating TM levels in SLE patients are enhanced. In addition, circulating TM levels may be practical in reflecting the disease activity and nephritis involvement of SLE patients.

Chemokine CXCL1 as a potential marker of disease activity in systemic lupus erythematosus

ObjectivesThe chemokine CXCL1, known as growth-related oncogene α (GRO-α), is a potent chemoattractant and regulator of neutrophils. The purpose of our study was to evaluate the regulatory response of CXCL1 in the serum of patients with systemic lupus erythematosus (SLE) in the active stage of disease and to assess whether it was implicated in the pathogenesis/inflammatory process in lupus.MethodsCXCL1 serum concentrations were examined in 90 SLE patients, 56 other autoimmune diseases (OADs) patients and 100 healthy controls using enzyme-linked immunosorbent methodology.ResultsSLE patients exhibited significant increases in serum CXCL1 concentrations [1492.86 (735.47–2887.34) pg/ml] compared with OADs patients [155.88 (10.77–366.78) pg/ml] and healthy controls [13.58 (8.46–37.22) pg/ml] (p < 0.001). Moreover, the level of CXCL1 decreased as the level of anti-dsDNA IgG decreased after treatment between the anti-dsDNA-positive SLE patients and the anti-dsDNA-negative SLE patients. Additionly, serum CXCL1 concentrations were related to different disease activity levels in SLE and lupus nephritis (LN) and high avidity of IgG ANAs (HA IgG ANAs) (p < 0.05). Furthermore, CXCL1 serum concentrations were significantly correlated with the SLE Disease Activity Index(SLEDAI) score, relative avidity index (RAI) of HA IgG ANAs and the levels of anti-dsDNA IgG, CRP, ESR, albumin, C3 and C4.Additionally, Statistical analysis revealed that positivity for IgG ANA (p < 0.001), the presence of HA IgG ANAs (p = 0.001) and the logarithmic level of anti-dsDNA IgG (p = 0.021) were significantly associated with the logarithmic level of CXCL1 with standard partial regression coefficients (95% CI) of 2.371 (1.734–3.009), 1.231 (0.52–1.937) and 0.409 (0.062–0.755), respectively. Finally, using cutoff points of 1182.17 pg/mL and 1500.31 pg/mL, serum CXCL1 levels had a similar sensitivity of 76% and specificity of 100% and 75% for the diagnosis of active SLE and LN, respectively.ConclusionsSerum CXCL13 concentrations might represent a potential marker of disease activity in systemic lupus erythematosus.

Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity.

Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4weeks post-vaccination. Disease activity and therapies were also evaluated. Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (www.clinicaltrials.gov, NCT03540823).