Systemic Lupus Erythematosus Disease Activity Index Research Articles

Exploring the interplay of MTHFR and FGG polymorphisms with serum levels of adiponectin and leptin in pediatric lupus nephritis: a pilot study

BackgroundAdiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN.MethodsNinety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs.ResultsCompared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01).ConclusionSerum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.

Intestinal permeability correlates with disease activity and DNA methylation changes in lupus patients

ObjectiveSystemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that can involve various organ systems. Several studies have suggested that increased intestinal permeability may play a role in the pathogenesis of lupus. The aim of this study was to elucidate the relationship between intestinal permeability, disease activity, and epigenetic changes in lupus patients. MethodsA total of 25 female lupus patients were included in this study. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were used as indicator of disease activity. Plasma zonulin levels were measured, using an ELISA, as a marker of intestinal permeability. Genome-wide DNA methylation patterns were assessed in neutrophils for 19 of the lupus patients using the Infinium MethylationEPIC array. Linear regression and Pearson's correlation were used to evaluate the correlation between zonulin concentrations and SLEDAI scores. The relationship between DNA methylation levels and zonulin concentrations was assessed using beta regression, linear regression, and Pearson's correlation, adjusting for age and race. ResultsIntestinal permeability positively correlated with disease activity in lupus patients (p-value = 7.60 × 10−3, r = 0.53). DNA methylation levels in 926 CpG sites significantly correlated with intestinal permeability. The highest correlation was identified in LRIG1 (cg14159396, FDR-adjusted p-value = 1.35 × 10−12, adjusted r2 = 0.92), which plays a role in intestinal homeostasis. Gene Ontologies related to cell-cell adhesion were enriched among the genes that were hypomethylated with increased intestinal permeability in lupus. ConclusionOur data suggest a correlation between increased intestinal permeability and disease activity in lupus patients. Further, increased intestinal permeability might be associated with epigenetic changes that could play a role in the pathogenesis of lupus.

Using combination of albumin to fibrinogen ratio and prognostic nutritional index model for predicting disease activity in patients with systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is chronic autoimmune disease with multiple organ damage and is associated with poor prognosis and high mortality. Identification of universal biomarkers to predict SLE activity is challenging due to the heterogeneity of the disease. This study aimed to identify the indicators that are sensitive and specific to predict activity of SLE.Methods: We retrospectively analyzed 108 patients with SLE. Patients were categorized into SLE with activity and without activity groups on the basis of SLE disease activity index. We analyzed the potential of routine and novel indicators in predicting the SLE activity using receiver operating characteristic curves and multivariate logistic regression. The Spearman method was used to understand the correlation between albumin to fibrinogen ratio (AFR), prognostic nutritional index (PNI), AFR-PNI model and disease activity.Results: SLE with activity group had higher ESR, CRP, D-dimer, fibrinogen, CRP to albumin ratio, positive rate of anti-dsDNA and ANUA, and lower C3, total bilirubin, total protein, albumin, albumin/globulin, creatinine, high density liptein cholesterol, hemoglobin, hematocrit, lymphocyte count, positive rate of anti-SSA, AFR, PNI than SLE without activity. A further established model based on combination of AFR and PNI (AFR-PNI model) showed prominent value in distinguishing SLE with activity patients from SLE without activity patients. In addition, the sensitivity and specificity of AFR-PNI model + anti-dsDNA combination model were superior to AFR-PNI model. AFR and PNI were risk factors for SLE activity. Moreover, AFR+PNI model correlated with disease activity and AFR-PNI model was associated with fever, pleurisy, pericarditis, renal involvement.Conclusion: These findings suggest that predictive model based on combination of AFR and PNI may be useful markers to identify active SLE in clinical practice.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Correlation of simple hematological parameters with disease activity and damage indices among Egyptian patients with systemic lupus erythematosus

ObjectiveTo evaluate the correlation of different hematological parameters in lupus patients with SLE disease activity index (SLEDAI), the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and some laboratory data related to kidney functions in active patients with nephritis. Material and methods80 inactive SLE patients (SLEDAI score<10 points), and 80 active patients (SLEDAI≥10 points) were enrolled in this study. All patients underwent full medical history taking, clinical evaluation including calculation of SLEDAI and SLICC/ACR DI scores, and laboratory investigations including complete blood count. The two groups were compared regarding different disease parameters. Correlations of some hematological parameters with SLEDAI, SLICC/ACR DI scores and some laboratory data related to kidney function in patients with nephritis were made. ResultsThe active group showed statistically significantly higher mean NLR (P=0.000), NC3R (P=0.000), MLR (P=0.000), PLR (P=0.000), and RDW (P=0.001), and statistically significantly lower mean MPV (P=0.002). The mean MLR (P=0.018) and PLR (P=0.005) were statistically significantly higher in the active patients with nephritis. For both groups, there were no significant correlations between studied parameters and SLEDAI or SLICC/ACR DI, except with NC3R values in the active group which were associated with SLEDAI (r=.221, P=0.049). ConclusionThe hematological parameters in SLE have promising potential clinical application as a novel activity marker, especially in patients with nephritis.

Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease

ObjectiveTo evaluate safety and mechanism of action of mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE).MethodsA phase 1b double-blind, placebo-controlled, multicentre study...

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice

Objective: Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. Methods: The proportions of CXC chemokine receptor (CXCR)4+ B cells and CFDA-labeled MRL/lpr-derived B cells were detected by flow cytometry. The levels of CXC chemokine ligand (CXCL)12in peripheral blood (PB)were measured by ELISA. The migrated B cells to osteoblasts (OBs) was measured by transwell migration assay. The relative spatial position of B cells, OBs and CXCL12 was presented by Immunofluorescence assay. Results: Firstly, we found that the percentage of CXCR4+ B cells was lower in PB and higher in the BM from both MRL/lpr mice and patientswith Systemic lupus erythematosus (SLE). Secondly, OBs from MRL/lpr mice produced more CXCL12 than that from C57BL/6 mice. Besides, MRL/lpr-derived OBs demonstrated more potent chemotactic ability toward B-lymphocytes than control OBs by vitro an vivo. Additionally, more B-lymphocytes were found to co-localize with OBs within the periosteal zone of bone in MRL/lpr mice. Lastly, the percentages of CXCR4+B cells were found to be negatively correlated with serum Immunoglobulin (Ig) G concentration, moreover, BM CXCL12 levels were found to be positively correlated with SLE disease activity index Score and negatively correlated with serum Complement3 (C3) concentration. Conclusions: our results indicated that there is a shifted distribution of B-lymphocytes between BM and peripheral compartments in both SLE patients and MRL/lpr mice. Besides, the up-regulated levels of CXCL12 in OBs was indicated to contribute to the enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.

Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Histone-Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus.

The aim of this study was to assess whether circulating histone-specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Seroprevalence of autoantibodies and HLA-DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA-peptide autoepitope couples for ex vivo detection of antigen-specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA-DRB1*03:01 and/or HLA-DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Histone-specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti-DNA antibodies, 77% had detectable histone-specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone-specific regulatory and effector T helper (Th) 1-, Th2-, and atypical Th1/Th17 (Th1*)-polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1-, Th2-, and Th1*-polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone-specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone-specific naive T (TN) and terminally differentiated T cells. Histone-specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.

Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte subsets balance

ObjectiveThe efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore,...

Adverse Impact of Systemic Lupus Erythematosus on Pregnancy Outcomes: A Saudi Arabia Retrospective Multi-Center Study.

The current study aimed to determine the pregnancy outcomes complications in patients with SLE and its association with clinical, laboratory variables, disease activity, and medication use in the Saudi population, as well as pregnancy effect on disease activity. A multicenter study included pregnant female patients with Systemic Lupus Erythematosus (SLE) from three tertiary centers in Saudi Arabia. The demographics, clinical, and laboratory variables, SLE disease activity index (SLEDAI), medication before, during, and after pregnancy, planned pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted. A total of 66 pregnant patients with SLE and 93 healthy age-matched pregnant controls were included in the study. A total of 77.3% had SLEDAI-2K ≤ 4 before conception, and 84.85% of pregnancies were planned. Age of conception, cesarean section, miscarriage, and low birth weight were statistically significant (p <0.05) higher in SLE patients than in healthy controls. Among all clinical and laboratory variables, SLEDAI-2K > 4 and active lupus nephritis during pregnancy were statistically associated with adverse outcomes (p <0.05), history of lupus nephritis was not associated with statistically adverse pregnancy outcomes. Higher SLEDAI-2K > 4 was an independent risk at least 4.87 times higher association with adverse pregnancy outcomes. (p <0.05). SLE is intricately connected with unfavorable pregnancy outcomes. The preconception of high disease activity stands as a pivotal risk factor for adverse outcomes. Despite the disease remission and meticulous planning, SLE patients frequently grapple with disease exacerbations during pregnancy, culminating in unexpected and unfavorable pregnancy-related outcomes. This underscores the intricate and multifaceted nature of managing SLE during gestation.

Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis

BackgroundJuvenile SLE (JSLE) is a complex autoimmune disorder that predominantly affects children and adolescents with several unique challenges, and microRNA-146a (miRNA-146a) might be an interesting anti-inflammatory molecule. Because exosomes in...

Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis

BackgroundLupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN.Aim of workInvestigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology.Patients and methodsA case–control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated.ResultsUrinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005).ConclusionUrinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4.Key Points• Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients.• It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN.• A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN.• Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.

Clinical significance of miR-200a in systemic lupus erythematosus and renal damage in children.

The purpose was to analyze the clinical significance of miR-200a in children with initially diagnosed SLE and renal damage. Children with initially diagnosed SLE (n=100) and healthy children (n=50) undergoing physical examinations during the same period were recruited. Disease activity of SLE children was determined based on SLEDAI (systemic lupus erythematosus disease activity index), and they were divided to SLEDAI≤9 group and SLEDAI>9 group, respectively. Moreover, SLE children were divided to LN group and non-LN group based on the occurrence of lupus nephritis. Differential level of miR-200a between groups was detected by qRT-PCR. Spearman correlation test was conducted to analyze the influence of miR-200a on SLEDAI and other laboratory indexes of SLE children. Its diagnostic potential in SLE and LN was assessed through depicting ROC curves. MiR-200a level was remarkably lower in SLE children than that of healthy children. Lower level of miR-200a was detected in SLE children with high SLEDAI or accompanied LN. MiR-200a level was negatively correlated to SLEDAI (r=-0.425), ESR (r=-0.284), CRP (r=-0.338), BUN (r=-0.263) and Scr (r=-0.345), while it was positively correlated to C3 (r=0.631), C4 (r=0.524) and ALB (r=0.394) in SLE children. The AUC of miR-200a in diagnosing SLE was 0.8379 (cut-off value=2.225, sensitivity=70%, specificity=70%). Besides, the AUC of miR-200a in diagnosing LN was 0.7619 (cut-off value=2.005, sensitivity=80%, specificity=76%). MiR-200a level has a certain correlation to the disease activity of children with initially diagnosed SLE, which can be utilized as an adjuvant indicator in evaluating SLE severity. Meanwhile, miR-200a has predictive value for SLE-induced renal damage.

GENE EXPRESSION AND SINGLE NUCLEOTIDE POLYMORPHISM (rs1140713) OF MICRORNA-126

MicroRNAs are non-coding gene regulators that may serve as systemic lupus erythematosus biomarkers for diagnosis or prognosis. This study was aimed to identify the single nucleotide polymorphism (rs1140713) of microRNA-126 and its expression by using PCR and qRT-PCR techniques. This research involved 100 womenwith SLE with a mean age of 32.85±9.992 years they were obtained from Baghdad city (medical city, Baghdad Hospital)/Iraq, along with 100 healthy controls with a mean age of 31.68±8.308 years. The mean score on the SLE disease activity index (SLEDAI-2k) was 10.860.±3.275 and a disease duration was 9.00 years, (Erythrocyte sedimentation rate, C-reactive protein, urea, and creatinine were all significantly higher in SLE patients compared to controls, while haemoglobin, white blood cells, complement 3, and complement 4 were significantly lower in contrast to controls (p-value=&lt; 0.0001**)). According to the examination of anti-nuclear antibodies (ANA) in patients, 89% of them have ANA and 95% have anti-double strand DNA (anti-dsDNA) antibodies. Single nucleotide polymorphism analysis for subjects involved in this study revealed a significant increased risk association between miRNA-126 (rs1140713) heterozygote (CT)(OR=20.64; p≤0.001) and homozygote mutant (TT) (OR = 16.35; p= 0.001) genotypes and SLE incidence. Moreover, the results showed a substantial decline in microRNA-126 expression with fold change mean (0.639±2.931) in comparison to controls' fold change mean (1.00±0.00). The present investigation found no indication of a relationship between changes in microRNA-126 folds and demographic or laboratory studies of the disease. The results suggest the microRNA-126 might consider as biomarkers in SLE pathogenesis.

Association of urine autoantibodies with disease activity in systemic lupus erythematosus.

The presence of urinary autoantibodies in patients with systemic lupus erythematosus (SLE) has been confirmed by several studies; however, the significance of their presence in urine remains unclear. This study aims to further investigate the association between urine autoantibodies and disease activity as well as organ involvement in SLE. This cross-sectional study included 89 SLE patients. Data collected included anti-nuclear antibody (ANA), anti-ENA antibodies, and anti-dsDNA antibody levels in both serum and urine, complement (C) 3, C4 levels in serum, SLE disease activity index-2000 (SLEDAI-2000), renal domains of SLEDAI (RSLEDAI) and non-renal SLEDAI (NRSLEDAI). The rate of positive urine ANA (uANA) was 33.3% (29/87) among the enrolled patients. Compared to the uANA negative group, the positive group exhibited significantly higher SLEDAI-2000 scores (7.85 ± 5.88 vs. 18.69 ± 6.93, p < 0.001), RSLEDAI scores [0 (0, 4.0) vs. 12.0 (8.0, 16.0), p < 0.001], and NRSLEDAI [4 (2.0, 8.0) vs. 6.0 (4.0, 9.5), p = 0.038]. Patients with positive urine anti-Sm antibody demonstrated significantly elevated SLEDAI-2000 scores compared to those who were negative (25.0 ± 8.80 vs. 10.09 ± 6.63, p < 0.001). Similarly, they also had higher RSLEDAI [16.0 (12.0, 16.0) vs. 4.0 (0, 8.0), p < 0.001] and NRSLEDAI [9.5 (6.0, 13.5) vs. 4.0 (3.0, 8.0), p = 0.012], as well as a greater prevalence of renal involvement compared to their negative counterparts (100% vs. 58.2, p = 0.022). There was a positive correlation between uANA titer and both SLEDAI-2000 (rs = 0.663, p < 0.001) and RSLEDAI (rs = 0.662, p < 0.001). The serum anti-dsDNA antibody level did not exhibit a significant correlation with RSLEDAI (rs = 0.143, p = 0.182). Conversely, the urine anti-dsDNA antibody level demonstrated a significant positive correlation with RSLEDAI (rs = 0.529, p < 0.001). Urine ANA is associated with both global SLEDAI and RSLEDAI scores. Urine anti-Sm antibody is associated with an increased incidence of renal involvement in SLE. The urine anti-dsDNA antibody level, rather than the serum anti-dsDNA antibody level, exhibits a significant association with RSLEDAI in SLE.

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.