Inactive Systemic Lupus Erythematosus Research Articles

Evaluation of Serum Amyloid A and some Biochemical markers in Iraqi patients with systemic lupus erythematosus

An autoimmune condition called systemic lupus erythematosus (SLE) is caused by long-term inflammation. Amyloid A (AA) amyloidosis results in nephropathy and other internal symptoms, including death. The current study set out to look at the relationship between serum amyloid A (SAA) levels in circulation and SLE patients. Methods: Sixty SLE patients and 30 healthy with age range (19-55) yearswere involved in this study. A SLE patient wasidentified in the teaching hospital in Baghdad. In this study, laboratory indicators such as blood lipid, kidney function, test results, and total cholesterol (TC), triglyceride (TG), SAA, and ALB were assessed using an automated biochemical analyzer. Results: Patients with active SLE had serum amyloid A (SAA) values 5.83 mg/L [IQR: 2.08–10.87], 4.92 mg/L [IQR: 1.57–11.43], and 1.33 mg/L [IQR: 0.13–3.12], respectively, substantially upper than personswith inactive SLE or healthy control subjects (P < 0.001). ESR values in healthy control subjects, patients with inactive SLE, and patients with active SLE. In conclusion, the current study's findings offered more proof of SAA's potential involvement in SLE and suggested that it might be valuable biomarkers that could reveal more details about the disease's activity.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression

ObjectiveTo investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). MethodsA case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. ResultsDiverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. ConclusionsEnvironmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. Statement of environmental implicationWe examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

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.

Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis

ObjectiveTo identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). MethodsUrine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. ResultsSystems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). ConclusionIn addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.

Clinical algorithm model based on cfDNA to predict SLE disease activity.

Circulating cell-free DNA (cfDNA) has been widely used as a new liquid-biopsy marker. Dysregulation of cfDNA has been found in patients with systemic lupus erythematosus (SLE). However, the detailed association between cfDNA and SLE has not been thoroughly studied. Plasma samples were collected from 88 patients with active SLE and 39 patients with inactive SLE. The cfDNA concentration was determined, and the length and distribution of cfDNA fragments were verified. cfDNA concentrations were significantly higher in patients with active SLE than in patients with inactive SLE (0.4 [0.18-0.897] ng/µL vs 0.249 [0.144-0.431] ng/µL; p = .043). cfDNA fragments were enriched in the ranges of 153-198 bp and 300-599 bp. cfDNA concentrations were associated with the reduction of the anti-double-stranded DNA (dsDNA) antibodies titer (r = -0.301, p = .034). The presence of anti-U1 ribonucleoprotein (p = .012), anti-Sjogren syndrome A (p = .024), anti-dsDNA (p = .0208), and anti-nucleosome antibodies (p = .0382) might associate to the variation of cfDNA concentration. Reduced cfDNA concentration was associated with renal damage in active SLE patients (0.31 [0.11-0.73] ng/µL vs 0.65 [0.27-1.53] ng/µL; p = .009). The Active index, a combination model including cfDNA concentration and other clinical indices, had an area of 0.886 under the receiver operating characteristics curve for distinguishing active SLE. The Active index was positively correlated with the SLE disease activity index score (r = 0.6724, p < .0001). Through systematic stratified analysis and clinical algorithm model, this study found that plasma cfDNA concentration is closely related to SLE disease severity, which has guiding significance for the future clinical application of cfDNA in SLE.

Levels of VCAM-1 and ICAM-1 in serum of active and inactive Systemic Lupus Erythematosus patients as biochemical markers for risk of cardiovascular disease

Background: Cardiovascular complications represent one of the consequences of chronic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), which has significant rates of morbidity and mortality. Dyslipidemia can be brought on by steroid medications, which are frequently given to SLE patients and are considered to be one of the major risk factors for cardiovascular diseases. Objectives: This study attempted to investigate a potential association between circulating vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) as risk factors for atherosclerosis and their relationship to cardiovascular risk. Patients and methods: A total of 100 patients and 50 apparently healthy controls were included in the study. All patients were from the Department of Rheumatology, Baghdad Hospital / Medical City during the period from 1 December 2021 to 1 March 2022 who were all treated with antimalarial drugs as immunosuppressants such as chloroquine (CQ) or hydroxychloroquine HCQ). They were divided according to the SLE disease activity index 2000 (SLEDAI-2K) into the active group (SLEDAI ≥ 10) and the inactive group (SLEDAI). Results: Serum VCAM and ICAM were significantly high in all study groups of SLE patients. The VCAM mean ± SD were (271.9±63.90), (247.9±82.92) and (97.7±24.69) in the active, inactive controls respectively. The ICAM mean ± SD were (3.1±0.91), (2.7±0.79) and (1.8±0.22) in the active, inactive and controls respectively. The values have increased gradually with increasing disease activity. The area under curve (AUC) of ICAM and VCAM were (0.802), (0.776) in active SLE patients and (0.858), (0.674) in inactive SLE patients. However, the AUC of VCAM and ICAM in active group were the highest. Conclusion: In SLE patients, VCAM-1 and ICAM-1 serum levels may operate as disease detection and severity differentiation indicators, and they may be linked to the number of coronary lesions in people at risk of developing CVD. Received: Aug.,2022 Accepted: Sept., 2022 Published: April 2023

Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis

ObjectiveTo determine if the serum levels of neutrophil extracellular trap (NET) remnants (Elastase-DNA and HMGB1-DNA complexes) at the time of a lupus nephritis (LN) flare predict renal outcomes in the...

Clinical utility of serum Galactin-9 in evaluation of systemic lupus erythematosus patients

Aim of the workTo evaluate the levels of serum Galactin-9 (Gal-9) in systemic lupus erythematosus (SLE) patients and to assess its association with disease activity, severity, and renal affection. Patients and methodsThe study included 50 SLE patients and 50 matched controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active (SLEDAI > 4) and inactive (SLEDAI ≤ 4). Renal affection in SLE patients was assessed by rSLEDAI. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) was assessed.Serum Gal-9 levels were measuredby Enzyme-Linked Immunosorbent Assay (ELISA). ResultsThe mean age of SLE patients was 31.1 ± 8.7 years and the majority of studied groups were females. Gal-9 was significantly higher in SLE patients in comparison to healthy control (890.1 ± 1740.4 vs. 266.8 ± 37.9 ng/L); p < 0.0001) and in active compared to inactive LN patients (1377.9 ± 2273.8 vs. 317.6 ± 40.4, P < 0.001) was detected. Serum Gal-9 correlated with anti-dsDNA positivity (r = 0.29, p = 0.04), SLEDAI (r = 0.61, p ≤ 0.0001), and rSLEDAI (r = 0.61, p ≤ 0.0001). At a cut-off value of 299 ng/l Gal-9 can significantly differentiate SLE patients from controls (AUC 0.97; p < 0.0001) at a sensitivity of 88 %, specificity of 75 %, and accuracy of 83.3 %. Gal-9 at a cut-off value 335 ng/l can significantly differentiate active from inactive SLE patients (AUC 0.94; p < 0.0001) at a sensitivity of 90 %, specificity of 84.2 %, and accuracy of 88 %. Gal-9 was significant predictor for SLE activity. ConclusionThe serum Gal-9 levels were significantly high in SLE patients compared to healthy controls and these high levels were associated with disease activityand renal affection in SLE patients.

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06). The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.

Assessment of peripapillary retinal nerve fiber layer thickness and vessel density in newly diagnosed SLE patients without ocular symptoms.

This study aims to assess peripapillary retinal nerve fiber layer thickness (pRNFLT) and peripapillary vessel density (PVD) in patients with newly diagnosed active and inactive systemic lupus erythematosus (SLE) by optical coherence tomography (OCT) and OCT angiography (OCTA). This is a cross-sectional study, in which 77 newly diagnosed SLE patients without ocular symptoms (including 36 active SLE patients and 41 inactive SLE patients) and 72 age- and gender-matched healthy subjects were recruited. All participants underwent OCT and OCTA to evaluate pRNFLT, PVD, and radial peripapillary capillary density (RPCD), respectively. Clinical data at the time of initial diagnosis of SLE, including erythrocyte, leukocyte, platelet, albumin-globulin ratio, erythrocyte sedimentation rate, C-reactive protein, serum complement 3, serum complement 4, anti-dsDNA antibody, and 24-h proteinuria, were collected. No difference was found in pRNFLT between active SLE patients, and healthy controls, average pRNFLT, superonasal RNFLT, and inferonasal pRNFLT were reduced in inactive SLE patients than in healthy controls (p≤0.008). Temporal PVD, inferotemporal PVD, and inferotemporal RPCD in active SLE patients were significantly lower than those in healthy controls (p≤0.043). There also was a trend towards lower temporal RPCD in active SLE than healthy controls (p=0.089). Average PVD, average RPCD, superonasal RPCD, inferonasal RPCD, and inferotemporal RPCD were decreased in inactive SLE patients than in healthy controls (p≤0.047). Additionally, inferotemporal RPCD in active SLE patients was positively associated with albumin-globulin ratio (p=0.041). Temporal RPCD was negatively correlated with anti-dsDNA antibody (p=0.012) and 24-h proteinuria (p=0.006). PRNFL and PVD damage existed in newly diagnosed SLE patients without ocular symptoms. Temporal and inferotemporal RPCD were associated with the laboratory indicators of impaired renal function in active SLE patients, respectively.

Soluble Receptor Level of Advanced Glycation (sRAGE) Products in Serum in Patients with Systemic Lupus Erythematosus:

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by antibody formation against nuclear autoantigens. Many molecules play a role in etiopathogenesis. A receptor for Advanced Glycation (RAGE) is produced by many immune system cells, such as neutrophils, macrophages, and T cells, and interacts with many classes of ligands. For example, studies have shown that the interaction of the receptor with the HMG1 (High mobility group box-1) ligand induces the production of type 1 interferon (IFN), which plays a crucial role in the pathogenesis of SLE. In light of these results, the level of sRAGE, the soluble form of RAGE, may be associated with disease activity. In light of this information, we aimed to evaluate whether there is a relationship between plasma sRAGE levels and SLE. Methods: Eighteen patients diagnosed with SLE (M/F: 1/17) and twenty-one patients without any disease diagnosis (M/F: 2/19) were included as the control group. Four patients were classified as inactive SLE and fourteen as active SLE according to the SLE Disease Activity Index (SLEDAI) classification criteria. In these patients, plasma sRAGE level was measured by ELIZA method using ELIZA (enzyme-linked immunosorbent assay) kit (BioVendor Research and Diagnostic Products). The data obtained were compared between the groups. Conclusion: The mean plasma sRAGE level was lower in patients with SLE than in healthy control patients but not statistically significant (p=0.966). Our study found a positive correlation between SLEDAI and sRAGE levels in patients with SLE (r=0.628, p=0.005). Although no significant correlation was found between patients with SLE, sRAGE levels were positively correlated between fourteen patients classified as active SLE and the control group. sRAGE levels were statistically significantly higher in patients with active SLE (r=0.695, p=0.001). Discussion: In our study, we found that plasma sRAGE levels in patients with SLE were lower than in healthy controls, but plasma sRAGE levels in patients with active SLE were higher than plasma sRAGE levels in patients with inactive SLE. We hypothesized that reduced sRAGE levels in patients with SLE could be explained by the depletion of this soluble receptor. sRAGE-ligand complexes have been suggested to be eliminated from the blood via the spleen and liver. It is also possible that sRAGE levels in SLE patients are adjusted by alternative splicing and proteinases, and this possibility needs to be clarified in future investigations. Our study differed from another similar study showing that blood sRAGE levels were higher in patients with SLE than in healthy controls. Blood sRAGE levels were significantly increased during active disease compared with patients with quiescent SLE. The medication use of the patients and the small number of patients may explain this discrepancy.

Association between levels of serum and urinary B cell-activating factor and systemic lupus erythematosus disease activity.

This study investigated the correlation between serum and urinary B cell-activating factor (BAFF) levels and systemic lupus erythematosus (SLE) disease activity. This case-control study was conducted with 87 participants between December 2020 and September 2021. Sixty-two SLE patients who fulfilled the eligibility criteria were enrolled. SLE patients were categorized into active (n=34) and inactive (n=28) groups based on their Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores. The control group consisted of 25 healthy subjects. Serum and urine samples were collected for the measurement of BAFF levels. Finally, the relationship between these variables and SLE disease activity was investigated. The mean age of active (SLEDAI-2K >4) and inactive (SLEDAI-2K ≤4) SLE patients and healthy individuals were 32.8±7.8, 32.5±6.8, and 31.7±7.8 years, respectively (p=0.62). The median serum BAFF (s-BAFF) and urinary BAFF (u-BAFF) in active lupus patients (10.4 [2.3] ng/mL and 8.2 [3.7] ng/mL, respectively) were significantly higher than in inactive lupus patients (6 (7.1) ng/mL and 1.7 (4.7) ng/mL, respectively; p<0.001) and the control group (3 (3.7) ng/mL and 1.6 (2.2) ng/mL, respectively; p<0.001). However, s-BAFF (p=0.07) and u-BAFF (p=0.43) did not significantly differ between the inactive group and the control group. A significant positive correlation was observed between s-BAFF (r=0.41 and p=0.001) and u-BAFF (r=0.78 and p<0.001) levels and the SLEDAI-2K score. There is a significant positive correlation between serum and urinary BAFF levels and SLE disease activity. Furthermore, significantly higher levels of s-BAFF and u-BAFF have been observed in patients with active lupus compared to inactive and healthy subjects, indicating a possible role for BAFF in the pathogenesis of SLE disease activity.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.

To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLEdisease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.

Neuropsychiatric manifestations and magnetic resonance spectroscopy of the brain in systemic lupus erythematosus patients

BackgroundNeuropsychiatric manifestations of lupus (NPSLE) are considered one of the major and most devastating lupus manifestations. The aim of this study was to assess the neuropsychiatric manifestations in systemic lupus erythematosus (SLE) patients and estimate the effectiveness of brain magnetic resonance spectroscopy (MRS) and anti-ribosomal P antibody test in early detection of NPSLE. This cross-sectional study was carried out on 50 SLE patients. Demographic, clinical, and therapeutic data were assessed. All patients were subjected to thorough rheumatological and neuropsychiatric evaluation. Serologic tests included antinuclear antibodies, anti-double-stranded DNA, and anti-ribosomal P protein antibodies. Radiologic evaluation included brain MRS.ResultsThe mean age was 26.9 ± 98.9 years; the median disease duration was 18 (0–108) months. Headache was the most common neurological symptom (40%). Depression was not detected in 29 patients (58%), mild in 15 patients (30%), and moderate in 6 patients (12%). Anti-ribosomal P antibody titer was significantly elevated in patients with active in comparison with those with inactive lupus disease (p = 0.026). Brain MRS showed a statistically significant reduction in N-acetylaspartate creatine ratio (NAA/Cr) among patients with active lupus disease (p = 0.015) with a statistically significant increase in choline creatine ratio (Cho/Cr) among patients with inactive lupus disease (p = 0.049). There was a statistically significant negative correlation between the level of NAA/Cr and anti-ribosomal P antibody titer among patients with active lupus disease (p < 0.001).ConclusionsHeadache is the most common neurological manifestation among SLE patients. Anti-ribosomal P antibody titer is elevated in active SLE patients. The changes of NAA/Cr and Cho/Cr in brain MRS can be of help to differentiate between the active and inactive SLE.

Megamonas funiformis, Plasma Zonulin, and Sodium Intake Affect C3 Complement Levels in Inactive Systemic Lupus Erythematosus.

The etiology of systemic lupus erythematosus (SLE) remains unclear, with both genetic and environmental factors potentially contributing. This study aimed to explore the relationship among gut microbiota (GM), intestinal permeability, and food intake with inflammatory markers in inactive SLE patients. A total of 22 women with inactive SLE and 20 healthy volunteers were enrolled, and dietary intake was assessed through 24-h dietary recalls. Plasma zonulin was used to evaluate intestinal permeability, while GM was determined by 16S rRNA sequencing. Regression models were used to analyze laboratory markers of lupus disease (C3 and C4 complement and C-reactive protein). Our results showed that the genus Megamonas was significantly enriched in the iSLE group (p < 0.001), with Megamonas funiformis associated with all evaluated laboratory tests (p < 0.05). Plasma zonulin was associated with C3 levels (p = 0.016), and sodium intake was negatively associated with C3 and C4 levels (p < 0.05). A combined model incorporating variables from each group (GM, intestinal permeability, and food intake) demonstrated a significant association with C3 complement levels (p < 0.01). These findings suggest that increased Megamonas funiformis abundance, elevated plasma zonulin, and higher sodium intake may contribute to reduced C3 complement levels in women with inactive SLE.

Functional Genome Analysis for Immune Cells Provides Clues for Stratification of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE. In particular, activation of the OXPHOS pathway is persistent in inactive SLE, and this activation is associated with organ damage. The finding that hydroxychloroquine (HCQ), which improves the prognosis of SLE, targets toll-like receptor (TLR) signaling upstream of OXPHOS suggests the clinical importance of this pathway. IRF5 and SLC15A4, which are regulated by polymorphisms associated with SLE susceptibility, are functionally associated with OXPHOS as well as blood interferon activity and metabolome. Future analyses of OXPHOS-associated disease-susceptibility polymorphisms, gene expression, and protein function may be useful for risk stratification of SLE.

Cell phenotypes as activity biomarkers in patients with Systemic Lupus Erythematosus

The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.

Urine Galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus.

Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI&nbsp;VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Correlation between serum β2-microglobulin level and systemic lupus erythematosus disease activity: A PRISMA-compliant meta-analysis.

Background:Numerous studies have explored whether serum beta 2-microglobulin (β2-MG) can be used as a biomarker for monitoring systemic lupus erythematosus (SLE) disease activity, but the results are conflicting. Therefore, we performed a systematic meta-analysis to further investigate the correlation between serum β2-MG level and SLE disease activity.Methods:PubMed, Web of Science, Embase, and CNKI databases were thoroughly searched for eligible studies through April 2022. Standardized mean differences with 95% confidence intervals (95% CIs) were used to depict the differences in serum β2-MG levels between groups compared in the studies. The correlation between serum β2-MG level and SLE disease activity was assessed using Fisher z-values.Results:Sixteen articles with combined 1368 SLE patients were included in this meta-analysis. Serum β2-MG levels were significantly higher in SLE patients than in healthy controls (pooled standardized mean difference: 3.98, 95% CI: 2.50–5.46, P < .01). In addition, patients with active SLE had an increased serum β2-MG concentration compared to their inactive SLE counterparts. Furthermore, a positive correlation was observed between serum β2-MG levels and SLE disease activity (pooled Fisher z = 0.78, 95% CI: 0.61–0.96, P < .01).Conclusions:This study suggests that patients with SLE have higher serum β2-MG levels than healthy controls and that serum β2-MG levels are positively correlated with SLE disease activity. Thus, serum β2-MG level may be a promising biomarker for monitoring SLE disease activity.