Female Systemic Lupus Erythematosus Research Articles

Endothelin-1 Correlates with Blood Pressure and Pulse Pressure in Females with Lupus Associated Hypertension

Systemic Lupus Erythematosus (SLE) is a common autoimmune disease that is classified by IgG complex deposition in end organs including the kidney, heart, and vasculature. SLE disproportionally affects women to men (9:1 ratio), with a high prevalence in African American women. Importantly, patients with an SLE diagnosis have common cardiovascular complications including hypertension. Importantly, numerous studies have reported that plasma and urinary endothelin-1 (ET-1) levels are elevated in patients with SLE or hypertension. However, few studies have investigated the role of the synergistic effects of SLE and hypertension on ET-1. Therefore, we hypothesized that women with SLE and hypertension would have elevated plasma ET-1 levels compared to SLE or hypertension alone. To investigate this, we recruited non-SLE non-HTN controls (n=8), non-SLE HTN (n=7), SLE non-HTN (n=5), and SLE-HTN (n=6) female human subjects and analyzed clinical and demographic characteristics, plasma ET-1, c-reactive protein (CRP), soluble vascular adhesion molecule-1 (sVCAM-1), and anti-Smith autoantibodies. We found that plasma ET-1 levels are significantly higher in African American compared to European American patients independent of SLE or blood pressure status (p=0.0182). When plasma ET-1 levels were correlated with age and body mass index (BMI), ET-1 had a positive association with age (r=0.4861;p=0.0118), but no correlation with BMI (r=0.2137;p=0.2945). When subjects we characterized by SLE diagnosis, we found that female subjects with SLE had elevated plasma ET-1 levels compared to non-SLE controls (p=0.0141). Next, we stratified subjects by blood pressure status and found that only SLE-HTN subjects had significantly elevated plasma ET-1 levels compared to non-SLE non-HTN controls (p=0.0005), and a trend for elevated ET-1 levels over SLE non-HTN (p=0.0799). Lastly, we correlated plasma ET-1 levels to offce systolic blood pressure, diastolic blood pressure and calculated pulse pressure. We found that plasma ET-1 positively associated with systolic blood pressure (r=0.5621;p=0.0035) and pulse pressure (r=0.5810;p=0.0023) but not diastolic blood pressure (r=0.3177;p=0.1217). These data demonstrate that plasma ET-1 levels associate with SLE diagnosis and blood pressure status in our cohort of female SLE human subjects. Further investigation of ET signaling should be done in SLE and SLE-HTN human subjects. Veterans Affairs Biomedical Laboratory Research & Development Career Development Award (CDA-2) 1IK2BX005605-01 to J.P.V.B, Medical University of South Carolina College of Medicine Program Project Grant to J.C.O and J.P.V.B., and Medical University of South Carolina Core Centers for Clinical Research Project Award P30AR072582 to M.A.C and J.P.V.B. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Galantamine Reduces Blood Pressure and Renal Injury in Female Angiotensin II-induced Hypertensive Mice

Inflammation is a known culprit in the development and progression of hypertension. The autoimmune disease, systemic lupus erythematosus (SLE), is an important model of hypertension in the setting of chronic kidney inflammation. We have shown that administration of an acetylcholinesterase inhibitor, galantamine, attenuates the hypertension, kidney inflammation, and kidney injury in female SLE mice by activating the vagally-mediated cholinergic anti-inflammatory pathway. Although SLE hypertension represents a specific population of patients, we hypothesized that galantamine would have similar anti-inflammatory effects in the angiotensin II (AngII)-induced hypertensive mouse, which more commonly models essential hypertension. Female C57BL/6 mice were implanted with minipumps at 9 weeks of age for subcutaneous delivery of either AngII (1000 ng/kg/min) or saline (controls), and galantamine hydrobromide (4 mg/kg/day) or vehicle, for 21 days. At 12 weeks, carotid catheters were implanted and mean arterial pressure (MAP) was measured in conscious mice for two consecutive days. Mice were then euthanized, and kidneys collected. Markers of kidney inflammation and injury, including interleukin (IL)-6 and kidney injury molecule (KIM)-1, were measured by ELISA and normalized to total kidney protein. MAP (mmHg) was higher in AngII-treated mice compared to controls (174±4 vs. 133±3; n=4-5, p=0.0023). Galantamine lowered MAP in AngII mice (157±8; n=7, p=0.2567) without altering MAP in controls (133±4; n=5, p=0.9999). Renal IL-6 (pg/μg) was not different between AngII and control mice (0.004±0.0001 vs. 0.005±0.0006; p=0.6685). Although galantamine lowered IL-6 in both groups, it was only significant in controls (0.003±0.0002; p=0.0134) and not AngII mice (0.003±0.0003; p=0.4677). Renal cortical KIM-1 (pg/μg) trended higher in AngII mice compared to controls (2.53±0.50 vs 0.63±0.16; p=0.0741). Galantamine lowered KIM-1 in AngII mice (1.18±0.39, p=0.2064), but not controls (1.45 ± 0.59; p=0.6285). In summary, galantamine protected female mice from hypertension and renal injury in a model of AngII hypertension. This suggests that acetylcholinesterase inhibitor therapy may be effective in patients with hypertension. Studies funded by NIH R01HL153703 and K01HL139859 for KWM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A case–control study on health-related quality of life of systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic rheumatic autoimmune condition that can cause a wide range of symptoms and problems that may affect the health-related quality of life. The main objective of the study was to assess the SLE burden by exploring the effect of the disease on health-related quality of life. The study consisted of 29 female SLE patients and 27 healthy female controls; they were matched for age and parity. A 36-item Short Form health survey questionnaire (SF-36) was used to collect data from participants through face-to-face interviews and to assess their health-related quality of life. SF-36 summary scores for the physical and mental components were decreased in the studied patients compared with controls; PCS was 28.81 ± 16.63, 77.25 ± 15.75 for cases and controls, respectively; and MCS was 32.75 ± 18.69, and 78.75 ± 10.63 for cases and controls, respectively (p < 0.05). The high correlation between the two dimensions characterizes this decrease. SLE negatively affected the quality of life of the patients. Measures such as lifestyle modifications, physical activity, and a healthy diet should be taken to improve the health-related quality of life in SLE patients. In addition, raising the patient’s awareness about the disease and its consequences could help to cope with the illness and engage in social and physical activities.

Sex-specific differences in ICOS+ T helper cell differentiation in systemic lupus erythematosus patients with low disease activity

Systemic lupus erythematosus (SLE) is a sex biased chronic autoimmune disease affecting predominantly females during reproductive ages. Changes in the ratio of inducible costimulatory molecule (ICOS)+ regulatory (Treg) and non-regulatory responder (Tresp) CD4+ T cells proved to be crucial for the occurrence of high disease activity. Here, we investigated how the differentiation of ICOS+CD45RA+CD31+ recent thymic emigrant (RTE) Tresps into CD45RA−CD31− memory Tresps affects the percentages of ICOS+ Tresps within total CD4+ T cells. Three different pathways (pathway 1 via CD45RA−CD31+ memory Tresps, pathway 2 via direct proliferation and pathway 3 via resting mature naïve CD45RA+CD31− (MN) cells) were examined in healthy controls and SLE remission patients separated by sex. In female SLE remission patients, immunosuppressive therapy inhibited the ICOS+ RTE differentiation via CD45RA−CD31+ memory Tresps and direct proliferation, leaving an age-independently increased differentiation into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps compared with healthy controls. Due to exhaustion of this pathway with age, no age-dependent change in the percentages of ICOS+ Tresps within total CD4+ T cells could be found. In contrast, no age-independently increased differentiation could be detected in men due to sufficient immunosuppression of all three pathways. This allowed an age-dependent differentiation of ICOS+ RTE Tresps into CD45RA−CD31− memory Tresps by conversion of resting MN Tresps, resulting in age-dependently increasing percentages of ICOS+ Tresps within total CD4+ T cells. We hypothesize that the sex-specific differential effect of immunosuppression on the differentiation of ICOS+ Tresps may explain the sex- and age-dependent occurrence of high disease activity.

Concentrated growth factor therapy as cosmetic treatment in discoid lupus erythematosus.

Discoid lupus erythematosus (DLE) is a disfigurement disease. The atrophic scar and hair loss of this disease are followed by cosmetic defects and profoundly impact psychological health. Concentrated growth factor (CGF) has been widely adopted in medical cosmetology. Here we report a 36-year-old female systemic lupus erythematosus patient with a 5-year history of alopecia in DLE, who was recommended for CGF therapy and experienced hair regrowth. We suggest that CGF may be an effective cosmetic treatment for DLE.

Genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus.

X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.

علاقة الانترلوكينات 37 و40 مع داء الذئبة الحمامية الجهازية في نساء مرضى عراقيات

The primary cause of systemic lupus erythematosus (SLE) is autoantibodies to self-antigens. Interleukin 37 (IL-37) and Interleukin 40 (IL-40) are important cytokines which may play a role in regulating inflammation and involved in pathogenesis of autoimmune diseases like SLE. This study was aimed the interleukin levels (IL-37 and IL-40) during systemic lupus erythematous (SLE) development in Iraqi female patients. The present study was conducted on 100 female SLE patients and 100 healthy female controls, with mean ages of patients and controls )32.85 ± 0.99 and 32.05 ± 0.91)years, respectively. Erythrocytes Sedimentation Rate (ESR) and C-reactive protein (CRP) were investigated in this study. Enzyme-linked immune sorbent assay(ELISA) kits examined levels of interleukins in the serum of patients and healthy controls. The results found that IL-37 levels in SLE patients were lower than in controls(23.39 ±0.92ng/mL vs48.02 ±0.46ng/mL), respectively, with a statistically significant. While serum IL-40 levels appeared to have a higher significant in patients compared with the healthy control (9.98 ±0.32ng/mL vs4.16 ±0.05ng/mL) respectively. Also, ESR and CRP was high significant in patients compared with healthy controls. In conclusion, these findings suggest that IL-40 and IL-37 could be used as a biomarker for SLE.

Nerve conduction study findings in females with systemic lupus erythematosus

Aim of the workTo investigate the frequency, characteristics, and associated factors of systemic lupus erythematosus-related peripheral neuropathy (SLE-PN) using nerve conduction study (NCS). Patients and methodsA retrospective chart review was conducted at the Rheumatology clinics of King Abdulaziz University Hospital, Jeddah, Saudi Arabia from 2016 to 2020. Eligibility included systemic lupus erythematosus (SLE) diagnosed patients with at least one NCS result in their clinical records. Demographic, clinical, and biological characteristics were collected. ResultsAmong 101 female SLE patients, abnormal NCS findings were observed in 11 (10.9%) patients. Of those with abnormal NCS, 27.3% showed mixed axonal and demyelinated motor neuropathy, 18.2% had sensory-motor axonal neuropathy, another 18.2% presented with axonal left common peroneal neuropathy, and the same percentage was observed for axonal sensory neuropathy. Comparisons between abnormal and normal NCS groups in a study population revealed that the abnormal NCS group had significantly higher proportions of non-Saudi nationality, lupus nephritis, seizures, and high SLICC DI. Furthermore, this group was associated with higher ANA titers and exhibited a non-significant trend towards increased positive anti-DNA frequency. Multivariate analysis identified non-Saudi nationality and the presence of end-organ damage as two significant predictors of SLE-related PN. ConclusionPeripheral neuropathy in SLE patients in Saudi Arabia is not uncommon, specifically those with heightened disease activity, organ damage, or disadvantaged socioeconomic backgrounds. Predominantly, the condition presents as axonopathy impacting sensory nerves, with possible motor involvement. The critical role of electrophysiological studies in early detection and improved patient management is high lightened.

Gut microbiota landscape and potential biomarker identification in female patients with systemic lupus erythematosus using machine learning.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that disproportionately affects women. Early diagnosis and prevention are crucial for women's health, and the gut microbiota has been found to be strongly associated with SLE. This study aimed to identify potential biomarkers for SLE by characterizing the gut microbiota landscape using feature selection and exploring the use of machine learning (ML) algorithms with significantly dysregulated microbiotas (SDMs) for early identification of SLE patients. Additionally, we used the SHapley Additive exPlanations (SHAP) interpretability framework to visualize the impact of SDMs on the risk of developing SLE in females. Stool samples were collected from 54 SLE patients and 55 Negative Controls (NC) for microbiota analysis using 16S rRNA sequencing. Feature selection was performed using Elastic Net and Boruta on species-level taxonomy. Subsequently, four ML algorithms, namely logistic regression (LR), Adaptive Boosting (AdaBoost), Random Forest (RF), and eXtreme gradient boosting (XGBoost), were used to achieve early identification of SLE with SDMs. Finally, the best-performing algorithm was combined with SHAP to explore how SDMs affect the risk of developing SLE in females. Both alpha and beta diversity were found to be different in SLE group. Following feature selection, 68 and 21 microbiota were retained in Elastic Net and Boruta, respectively, with 16 microbiota overlapping between the two, i.e., SDMs for SLE. The four ML algorithms with SDMs could effectively identify SLE patients, with XGBoost performing the best, achieving Accuracy, Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and AUC values of 0.844, 0.750, 0.938, 0.923, 0.790, and 0.930, respectively. The SHAP interpretability framework showed a complex non-linear relationship between the relative abundance of SDMs and the risk of SLE, with Escherichia_fergusonii having the largest SHAP value. This study revealed dysbiosis in the gut microbiota of female SLE patients. ML classifiers combined with SDMs can facilitate early identification of female patients with SLE, particularly XGBoost. The SHAP interpretability framework provides insight into the impact of SDMs on the risk of SLE and may inform future scientific treatment for SLE.

Leptin antagonism attenuates hypertension and renal injury in an experimental model of autoimmune disease.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by B- and T-lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin. Leptin has various immunomodulatory properties, including promoting the expansion of proinflammatory T lymphocytes and the proliferation and survival of B cells. In the present study, we hypothesized that leptin antagonism would improve B- and T-cell dysfunction and attenuate hypertension in an experimental model of SLE, the NZBWF1 mouse. To test this hypothesis, 28-week-old female control and SLE mice were administered 5 mg/kg of murine leptin superantagonist (LA) or vehicle via ip injection every other day for four weeks. Analysis of peripheral blood immune cell populations showed no changes in total CD45R+ B and CD3+ T cell percentages after treatment with LA. However, SLE mice treated with LA had an improved CD4/CD8 ratio and decreased CD3+CD4-CD8- double negative (DN) T cells. Blood pressure was higher in SLE than in control, and treatment with LA decreased blood pressure in SLE mice. Treatment with LA also delayed the onset of albuminuria and decreased glomerulosclerosis in SLE mice. Renal immune cell infiltration was significantly higher in SLE mice as compared with control, but LA treatment was associated with decreased levels of renal CD4+ T cells. In conclusion, these data suggest that leptin plays a pathogenic role in the development of hypertension in SLE, in part, by promoting the expansion of inflammatory DN T cells and the infiltration of T cells into the kidneys.

Systemic lupus erythematosus patients have unique changes in serum metabolic profiles across age associated with cardiometabolic risk.

Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). Serum NMR metabolomic profiles from female SLE patients (n = 164, age = 14-76) and HCs (n = 123, age = 13-72) were assessed across age by linear regression and by age group between patients/HCs (Group-1, age ≤ 25, n = 62/46; Group-2, age = 26-49, n = 50/46; Group-3, age ≥ 50, n = 52/31) using multiple t-tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group-1), increased very-low-density lipoproteins (Group-2), and increased low-density lipoproteins (Group-3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein(Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type-1 and type-2 diabetes by disease-wide association. Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies.

Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study.

Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated. There were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858). Our findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.

The XIST lncRNA is a sex-specific reservoir of TLR7 ligands in SLE.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a dramatic sex bias, affecting 9 times more women than men. Activation of Toll-like receptor 7 (TLR7) by self-RNA is a central pathogenic process leading to aberrant production of type I interferon (IFN) in SLE, but the specific RNA molecules that serve as TLR7 ligands have not been defined. By leveraging gene expression data and the known sequence specificity of TLR7, we identified the female-specific X-inactive specific transcript (XIST) long noncoding RNA as a uniquely rich source of TLR7 ligands in SLE. XIST RNA stimulated IFN-α production by plasmacytoid DCs in a TLR7-dependent manner, and deletion of XIST diminished the ability of whole cellular RNA to activate TLR7. XIST levels were elevated in blood leukocytes from women with SLE compared with controls, correlated positively with disease activity and the IFN signature, and were enriched in extracellular vesicles released from dying cells in vitro. Importantly, XIST was not IFN inducible, suggesting that XIST is a driver, rather than a consequence, of IFN in SLE. Overall, our work elucidated a role for XIST RNA as a female sex-specific danger signal underlying the sex bias in SLE.

Clustering of systemic lupus erythematosus mortality in southwestern Spain.

To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001-2020). We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001-2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff's spatial scan statistic were used to identify clusters. Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest). We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.

Functional Brain Network Alterations in Patients With Systemic Lupus Erythematosus With Different Cognitive Function States: A Graph Theory Analysis Study.

The study aimed to investigate the characteristics of brain functional network disruption in patients with systemic lupus erythematosus (SLE) with different cognitive function states by using graph theory analysis and to explore their relationship with clinical data and neuropsychiatric scales. Resting-state functional magnetic resonance imaging data were collected from 38 female SLE patients and 44 healthy controls. Based on Montreal Cognitive Assessment (MoCA) scores, SLE patients were divided into a high MoCA group (MoCA-H; MoCA score, ≥26) and a low MoCA group (MoCA-L; MoCA score, <26). The matrix of resting-state functional brain networks of subjects in the 3 groups was constructed by using the graph theory approach. The topological properties of the functional brain networks, including global and local metrics, in the 3 groups were calculated. The differences in the topological properties of networks between the 3 groups were compared. In addition, Spearman correlation analysis was used to explore the correlation between altered topological properties of brain networks and clinical indicators, as well as neuropsychiatric scales in SLE patients in the MoCA-L group. At the global level, in the sparsity threshold range of 0.10 to 0.34, the values of small-world properties were greater than 1 in all 3 groups, indicating that functional brain networks of both 3 groups had small-world properties. There were statistically significant differences in the characteristic path length, global, and local efficiency between 3 groups ( F = 3.825, P = 0.0260; F = 3.722, P = 0.0285; and F = 3.457, P = 0.0364, respectively). Systemic lupus erythematosus patients in the MoCA-L group showed increased characteristic path length ( t = 2.816, P = 0.00651), decreased global ( t = -2.729, P = 0.00826), and local efficiency ( t = -2.623, P = 0.0109) compared with healthy controls. No statistically significant differences in local metrics were found between the MoCA-H group and the healthy control, MoCA-L groups. At the local level, there was statistically significant difference in the node efficiency among the 3 groups ( P < 0.05 after Bonferroni correction). Compared with healthy controls, SLE patients in the MoCA-L group showed decreased node efficiency in left anterior cingulate paracingulate gyrus, bilateral putamen, bilateral pallidum, and left Heschl gyrus. No statistically significant differences in the local metrics were found between the MoCA-H, MoCA-L, and healthy control groups. Correlation analysis in SLE patients in the MoCA-L group showed that the characteristic path length was positively correlated with C4 levels ( r = 0.587, P = 0.007), the global and local efficiencies were negatively correlated with C4 levels ( r = -0.599, P = 0.005; r = -0.599, P = 0.005, respectively), and the node efficiency in the bilateral putamen was negatively correlated with C4 levels ( r = -0.611, P = 0.004; r = -0.570, P = 0.009). The node efficiency in the left pallidum was negatively correlated with disease duration ( r = -0.480, P = 0.032). The node efficiency in the left Heschl gyrus was negatively correlated with IgM levels ( r = -0.478, P = 0.033). No correlation was noted between other network metrics, clinical indicators, and neuropsychological scales. The topological properties of functional brain networks were disrupted in SLE patients with low MoCA scores, suggesting that altered topological properties of the brain networks were associated with cognitive function in SLE patients. Correlation between altered topological properties of the brain networks and clinical indicators was noted in SLE patients with low MoCA scores, suggesting that altered topological properties of brain networks in SLE patients may have clinical significance as imaging markers for monitoring disease changes in patients with SLE.

Gender Disparities in Hospitalization Outcomes and Healthcare Utilization Among Patients with Systemic Lupus Erythematosus in the United States.

Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various clinical manifestations. Despite efforts to improve outcomes, mortality rates remain high, and certain disparities, including gender, may influence prognosis and mortality rates in SLE. This study aims to examine the gender disparities in outcomes of SLE hospitalizations in the US. Methods We conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) database between 2016 and 2020. The NIS database is the largest publicly available all-payer database for inpatient care in the United States, representing approximately 20% of all hospitalizations nationwide. We selected every other year during the study period and included hospitalizations of adult patients (≥18 years old) with a primary or secondary diagnosis of SLEusing International Classification of Diseases, Tenth Revision (ICD-10) codes. The control population consisted of all adult hospitalizations. Multivariate logistic regression was used to estimate the strength of the association between gender and primary and secondary outcomes. The regression models were adjusted for various factors, including age, race, median household income based on patients' zip codes, Charlson comorbidity index score, insurance status, hospital location, region, bed size, and teaching status. To ensure comparability across the years, revised trend weights were applied as the healthcare cost and use project website recommends. Stata version 17 (StataCorp LLC, TX, USA) was used for the statistical analyses, and a two-sided P-value of less than 0.05 was considered statistically significant. Results Among the 42,875 SLE hospitalizations analyzed, women accounted for a significantly higher proportion (86.4%) compared to men (13.6%). The age distribution varied, with the majority of female admissions falling within the 30- to 60-year age range, while most male admissions fell within the 15- to 30-year age category. Racial composition showed a slightly higher percentage of White Americans in the male cohort compared to the female cohort. Notably, more Black females were admitted for SLE compared to Black males. Male SLE patients had a higher burden of comorbidities and were more likely to have Medicare and private insurance, while a higher percentage of women were uninsured. The mortality rate during the index hospitalization was slightly higher for men (1.3%) compared to women (1.1%), but after adjusting for various factors, there was no statistically significant gender disparity in the likelihood of mortality (adjusted odds ratio (aOR): 1.027; 95% confidence interval (CI): 0.570-1.852; P=0.929). Men had longer hospital stays and incurred higher average hospital costs compared to women (mean length of stay (LOS): seven days vs. six days; $79,751 ± $5,954 vs. $70,405 ± $1,618 respectively). Female SLE hospitalizations were associated with a higher likelihood of delirium, psychosis, and seizures while showing lower odds of hematological and renal diseases compared to men. Conclusion While women constitute the majority of SLE hospitalizations, men with SLE tend to have a higher burden of comorbidities and are more likely to have Medicare and private insurance. Additionally, men had longer hospital stays and incurred higher average hospital costs. However, there was no significant gender disparity in the likelihood of mortality after accounting for various factors.

Characterization of virus-mediated autoimmunity and the consequences for pathological process in patients with systemic lupus erythematosus.

This study aimed to identify differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus (GEO) database. The significantly enriched immune and virus-related gene lists were computed and visualized by using the DEGs from the gene set enrichment analysis (GSEA). Quantification of 38 immune cells was performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQuant algorithm. Thirty-nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways in 26 female SLE patients. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein-Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. Identifying virus-mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of female SLE, and will lead to clinical tools for treating SLE in patients. Key Points • Using gene expression-based computational methodologies,the 57immune and viral genes were significantly upregulated in 26 SLE patients. • The identifiedthree key viral genessuch as OAS1, OAS2, and IF7 were closely associated with colony-forming unit-monocytes and colony-forming unit-granulocytes, which affect the virus mediated immunity in SLE. • The viral genes and quantifies of immune cells are useful in understanding pathogenesis of SLE, and this will provide clinical strategiesof potential treatment choicesin SLE patients.

Healthcare Costs and Utilization for Patients With Systemic Lupus Erythematosus in China: A National Claims Database Study

ObjectivesThis study aimed to describe the healthcare resource utilization (HCRU) and healthcare costs associated with systemic lupus erythematosus (SLE) management in China from the patient’s and the payer’s perspective. MethodsHCRU and medical costs (2017 US dollar [USD]) between January 1 and December 31, 2017, were extracted from the national medical insurance claims database, China Health Insurance Research Association (consisting of claims from all public health insurance schemes in China), for adults with ≥ 1 SLE-related claim. The main analysis group comprised all adults with an SLE diagnosis and claim during 2017 (overall group); the annual subgroup (SLE diagnosis and claim in January 2017) informed annual HCRU and costs. ResultsThe overall group consisted of 3645 adults with ≥ 1 SLE-related claim. Outpatient visits constituted 86.9% of healthcare visits. SLE-related healthcare outpatient costs were USD 433 per outpatient, and inpatient costs were USD 2072 per inpatient. Medication costs accounted for 75.0% (USD 42/56) of total costs for outpatient visits and 44.3% (USD 456/1030) for inpatient hospitalizations. Notably, 35.4% of patients had a severe SLE flare; mean SLE-related cost per severe flare was USD 1616. HCRU and costs were similar in the annual subgroup. Female sex, SLE flares, tertiary hospitals, renal involvement, and utilization of anti-infective drugs were associated with higher SLE-related patient costs. ConclusionsSLE in China is associated with considerable HCRU and medical costs, especially for patients experiencing severe SLE flares. Preventing organ involvement, infections, flares, and associated hospitalizations may reduce the burden on patients and healthcare providers in China.

Environmental risk factors of systemic lupus erythematosus: a case–control study

Systemic lupus erythematosus (SLE) is a complicated chronic autoimmune disorder. Several genetic and environmental factors were suggested to be implicated in its pathogenesis. The main objective of this study was to examine how exposure to selected environmental factors was associated with SLE risk to support the development of disease preventive strategies. A case–control study was conducted at the Rheumatology outpatient clinic of Alexandria Main University Hospital, in Alexandria, Egypt. The study sample consisted of 29 female SLE patients, and 27 healthy female controls, who matched the cases on age and parity. Data were collected by a structured interviewing questionnaire. Blood levels of lead, cadmium, and zinc of all participants were assessed by flame atomic absorption spectrometry. The multivariate stepwise logistic regression model revealed that five factors showed significant association with SLE, namely living near agricultural areas, passive smoking, blood lead levels ≥ 0.075 mg/L, and exposure to sunlight (odds ratio (OR) 58.556, 95% confidence interval (CI) 1.897–1807.759, OR 24.116, 95% CI 1.763–329.799, OR 18.981, 95% CI 1.228–293.364, OR 9.549, 95% CI 1.299–70.224, respectively). Whereas walking or doing exercise were significantly protective factors (P = 0.006). The findings of this study add to the evidence that SLE can be environmentally induced. Preventive measures should be taken to address the environmental risk factors of SLE.