Systemic Lupus Erythematosus Damage Research Articles

Indexes of skin activity and damage in patients with systemic lupus erythematosus – CLASI and R-CLASI

Introduction. Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version, the Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index (R-CLASI) are tools for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus and its systemic variant. Evaluation of the scales of activity and skin damage in systemic lupus erythematosus (SLE) is associated with the need to stratify their quantitative characteristics. The Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (R-CLASI) are a tool for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus (CLE) and its system version.Objective. To validate the indexes of objective assessment of skin activity and damage CLASI and R-CLASI in the Russian cohort of patients with systemic lupus erythematosus and compare it with dermatological assessments of the quality of life.Material and methods. The study included 55 patients with SLE with various types of skin and mucosal lesions, the median age was 30.0 [26.0; 40.0] years, the duration of the disease was 7.0 [3.0; 14.0] years. To assess the active (reversible) lesion and irreversible skin damage, the CLASI and R-CLASI indexes were used, for the general assessment of activity and damage in SLE, the SLEDAI-2K and SLICC/ACR DI were used.Results. The most common variant of skin lesions in patients with SLE is acute cutaneous lupus erythematosus (ACLE) – 45%, as well as alopecia, which occurs in 62% of cases. The median activity index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 7.0 [3.0; 18.0]; the median damage index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 2.0 [0.0; 7.0]. A significant relationship was revealed between the medians of CLASI and R-CLASI scores depending on the degree of activity according to SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) and the damage Index (DI) in SLE (SLICC/ACR DI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) when recalculating these indexes only for skin and mucous lesions. According to the ROC analysis, the CLASI and R-CLASI skin activity and damage indices showed high sensitivity (CLASI activity index – 98%, R-CLASI – 93%, CLASI and R-CLASI damage index – 91%) and specificity (CLASI activity index – 64%, R-CLASI – 71%, CLASI and R-CLASI damage index – 86%).Conclusion. To assess the severity of skin and mucosal lesions in patients with SLE in the Russian Federation, it is reasonable to use the CLASI and R-CLASI indices. The CLASI and R-CLASI indices reflect the level of activity and severity of skin lesions, with higher values of these indices indicating more severe skin lesions and a significant impact on the overall well-being of SLE patients. Patients with high values of these indices often experience feelings of embarrassment, discomfort, difficulty in performing daily tasks, and limitations in social life. To assess the severity of skin and mucous lesions in patients with SLE in the Russian Federation, it is advisable to use the CLASI and R-CLASI indexes.

Regulatory T cells and Disease damage in systemic lupus erythematosus

Regulatory T cells and Disease damage in systemic lupus erythematosus

Mean Platelet Volume Is Related to Cumulative Disease Damage in Patients with Systemic Lupus Erythematosus.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in 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.

Predictors of Organ Damage in Systemic Lupus Erythematosus in the Asia Pacific Region: A Systematic Review.

Irreversible organ damage is common in patients with systemic lupus erythematosus (SLE). Despite evidence of increased prevalence and severity of SLE in Asia Pacific, organ damage is less well studied in this region. This systematic review aims to identify predictors of organ damage in SLE in the Asia Pacific region. We searched Medline, PubMed, Embase, and Web of Science for observational studies on organ damage in adult patients with SLE in Asia Pacific from August 31, to September 5, 2022. Study selection and data extraction were completed by two independent reviewers using Covidence systematic review software. Risk of bias was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute tool. Significant results from univariable and multivariable analyses were synthesized from included studies. Thirty-eight eligible studies were selected from 1999 to 2022; 22 (58%) of these reported organ damage at study enrollment and 19 (50%) reported damage accrual, as measured by the Systemic Lupus International Collaborating Clinic/American College of Rheumatology Damage Index. Factors predictive of organ damage included older age, glucocorticoid use, longer disease duration, and disease activity. Lupus nephritis was a risk factor for renal and overall damage accrual. Hydroxychloroquine was protective against overall organ damage. Predictors of organ damage in SLE in Asia Pacific are similar to other regions. Although glucocorticoid use is a modifiable risk factor for organ damage, the impact of immunosuppressives and biologic therapies needs further investigation. Effective strategies in early disease are needed to minimize initial organ damage as it predicts subsequent damage accrual.

Comprehensive analysis of lactate-related gene profiles and immune characteristics in lupus nephritis.

The most frequent cause of kidney damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN), which is also a significant risk factor for morbidity and mortality. Lactate metabolism and protein lactylation might be related to the development of LN. However, there is still a lack of relative research to prove the hypothesis. Hence, this study was conducted to screen the lactate-related biomarkers for LN and analyze the underlying mechanism. To identify differentially expressed genes (DEGs) in the training set (GSE32591, GSE127797), we conducted a differential expression analysis (LN samples versus normal samples). Then, module genes were mined using WGCNA concerning LN. The overlapping of DEGs, critical module genes, and lactate-related genes (LRGs) was used to create the lactate-related differentially expressed genes (LR-DEGs). By using a machine-learning algorithm, ROC, and expression levels, biomarkers were discovered. We also carried out an immune infiltration study based on biomarkers and GSEA. A sum of 1259 DEGs was obtained between LN and normal groups. Then, 3800 module genes in reference to LN were procured. 19 LR-DEGs were screened out by the intersection of DEGs, key module genes, and LRGs. Moreover, 8 pivotal genes were acquired via two machine-learning algorithms. Subsequently, 3 biomarkers related to lactate metabolism were obtained, including COQ2, COQ4, and NDUFV1. And these three biomarkers were enriched in pathways 'antigen processing and presentation' and 'NOD-like receptor signaling pathway'. We found that Macrophages M0 and T cells regulatory (Tregs) were associated with these three biomarkers as well. Overall, the results indicated that lactate-related biomarkers COQ2, COQ4, and NDUFV1 were associated with LN, which laid a theoretical foundation for the diagnosis and treatment of LN.

Urinary biomarkers associated with podocyte injury in lupus nephritis.

The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN.

Vascular damage in systemic lupus erythematosus.

Vascular disease is a major cause of morbidity and mortality in patients with systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE). Although comorbid cardiovascular risk factors are frequently present in patients with SLE, they do not explain the high burden of premature vascular disease. Profound innate and adaptive immune dysregulation seems to be the primary driver of accelerated vascular damage in SLE. In particular, evidence suggests that dysregulation of type 1 interferon (IFN-I) and aberrant neutrophils have key roles in the pathogenesis of vascular damage. IFN-I promotes endothelial dysfunction directly via effects on endothelial cells and indirectly via priming of immune cells that contribute to vascular damage. SLE neutrophils are vasculopathic in part because of their increased ability to form immunostimulatory neutrophil extracellular traps. Despite improvements in clinical care, cardiovascular disease remains the leading cause of mortality among patients with SLE, and treatments that improve vascular outcomes are urgently needed. Improved understanding of the mechanisms of vascular injury in inflammatory conditions such as SLE could also have implications for common cardiovascular diseases, such as atherosclerosis and hypertension, and may ultimately lead to personalized therapeutic approaches to the prevention and treatment of this potentially fatal complication.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

Systemic Lupus Erythematosus, Antiphospholipid Syndrome: Focus on Nervous System Lesions

Systemic lupus erythematosus and antiphospholipid syndrome are two rare and complex diseases that can affect various organs and systems of the human body. Systemic lupus erythematosus is the prototype of connective tissue diseases that can present with a full spectrum of neurological and mental disorders. It is quite difficult to establish an accurate etiological diagnosis of systemic lupus erythematosus with predominant neuropsychiatric symptoms. The exact timing of neurological manifestations remains controversial: either the central nervous system is the initial target of autoimmune disorders, or neurological symptoms are part of a multisystem lesion. Antiphospholipid syndrome is a prothrombotic systemic autoimmune disease with heterogeneous clinical and pathological manifestations and is a well-established cause of ischemic stroke and transient ischemic attack, especially in young patients. There is growing recognition of a broader spectrum of cerebrovascular lesions associated with antiphospholipid syndrome, including white matter hyperintensities, cortical atrophy, and lacunar infarcts, which may have clinically important neurocognitive consequences. The article provides a review of the literature examining the spectrum of neurological disorders in patients with antiphospholipid syndrome and the inflammatory and cytokine mechanisms that play an important role in the pathogenesis of nervous system damage in systemic lupus erythematosus.

COX5A as a potential biomarker for disease activity and organ damage in lupus.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with limited therapeutic targets or clinical outcome predictors. This study aimed to gain more insights into the underlying immunological pathways and prognostic biomarkers of SLE. Integrated analyses of RNA-seq data from 64 SLE and 62 healthy controls, examining 27 immune cell types to explore the key pathways and driver genes in SLE pathogenesis. Single-cell RNA sequencing data from the skin and kidney were used to determine the association of COX5A expression with organ damage. The associations of COX5A with SLE phenotypes were further evaluated in two independent cohorts, and receiver operating characteristic (ROC) curves were constructed to assess the value of COX5A as a biomarker for disease activity and organ damage in SLE. We found that oxidative phosphorylation (OXPHOS) is the most significantly altered metabolic pathway in SLE, especially in effector T cells. Notably, we identified an OXPHOS-related enzyme, COX5A, whose expression was significantly higher in effector T cells than in naïve T cells and showed associations with disease activity, organ damage, and steroid treatment of SLE. Furthermore, ROC curves showed that COX5A is a robust biomarker for disease activity, kidney involvement, and new-onset skin lesions, with the area under the curve (AUC) values of 0.880, 0.801, and 0.805, respectively. Our results identified the OXPHOS signature as a prominent feature in SLE T cells, and COX5A as a potential candidate biomarker for disease activity and organ damage in SLE.

The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

N-Terminal pro-Brain Natriuretic Peptide is a biomarker for cardiovascular damage in systemic lupus erythematous: a cross-sectional study.

Prediction models based on traditional risk factors underestimate cardiovascular (CV) risk in systemic lupus erythematosus (SLE). In a large sample of unselected SLE patients, we investigated cross-sectional associations of NT-proBNP with cardiovascular damage (CVD). Serum NT-proBNP was measured in SLE patients enrolled in the MUHC Lupus Clinic registry. Serum were collected between March 2022 and April 2023 at annual research visits. The primary outcome was CVD identified on the SLICC Damage Index. Factors associated with CVD and NT-proBNP levels were determined. Overall, 270 SLE patients (female 91%, median age 50.7 [1st quartile- 3rd quartile : 39.6-62.1] years) were analyzed for the primary outcome. Among them, 33 (12%) had CVD. The ROC curve for NT-proBNP demonstrated strong associations with CVD (AUC 0.78, 95% CI 0.69-0.87) with a threshold of 133 pg/ml providing the best discrimination for those with/without CVD. Hypertension (OR 3.3, 95% CI 1.2-9.0), dyslipidaemia (OR 3.6, 95% CI 1.3-9.6) and NT-proBNP > 133 pg/ml (OR 7.0, 95% CI, 2.6-19.1) were associated with CVD in the multivariable logistic regression model. Increased NT-proBNP levels were associated with age (OR 4.2, 95% CI 2.2-8.3), ever smoking (OR 1.9, 95% CI 1.0-3.5), reduced eGFR (4.1, 95% CI 1.3-13.1), prior pericarditis/pleuritis (OR 2.5, 95% CI 1.4-4.5) and aPL antibodies (OR 2.6, 95% CI 1.4-4.9). NT-proBNP is a biomarker for CV damage in SLE. The novel associations of NT-proBNP levels with prior pericarditis/pleuritis and aPL antibodies suggest new avenues for research to better understand what drives CV risk in SLE.

Складнощі діагностики в дебюті системного червоного вовчака в дітей

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease that is more severe in children than in adults. The mortality of patients with SLE without treatment reaches 95.3% during the first 5 years from the onset of the disease. SLE develops more often in women. The ratio between girls and boys affected by SLE in prepubertal age is approximately 4.5:1 - 5:1, and in pubertal age - 9:1 - 10:1. Purpose - to show, on the basis of clinical observation, the difficulties of diagnosis and treatment in the debut of SLE in children. Clinical case. A 16-year-old child was treated in the children’s department of Road Hospital No. 1 with a diagnosis of «acute glomerulonephritis with leading incomplete nephrotic syndrome, hematuria, hypertension, tubulointerstitial component; a period of extensive clinical manifestations, with impaired kidney function. Postazotemic anemia. Secondary myelosuppression». She was admitted with complaints of swelling of the legs and face, changes in urine tests (proteinuria 1.65 g/day, leukocyturia 45-50 in the field of vision, erythrocyturia 35-40-50 in the field of vision). She considered herself sick when she noticed swelling of the ankle joints. Three weeks before admission to the hospital, she suffered acute pharyngitis (negative antistreptolysin O titer). Allergological history is not burdensome. At 6 years old - chicken pox. The child was prescribed corticosteroid therapy (prednisolone 50 mg/day), against the background of which, in the 4th week, the creatinine level normalized, but hypoproteinemia, elevated cholesterol, and proteinuria persisted, which indicated the lack of effect from CS therapy. Cytostatic therapy was started (leukeran - 8 mg/day (3 weeks); 4 mg/day - 3 weeks). Despite complex therapy, the child developed complete nephrotic syndrome, kidney failure six months later. During the examination of the patient, antinuclear antibodies with a titer &gt;80 were detected, which gave rise to the calculation of additional criteria points (17 points) in accordance with the diagnostic criteria for SLE proposed by the European Antirheumatic League (EULAR) and the American College of Rheumatology (ACR), 2019. A diagnosis was made: SLE. Lupus nephritis, nephrotic syndrome, period of extensive clinical manifestations. Arterial hypertension; anemia I st. severity; azotemia; 2-3 degree of activity of the pathological process. Conclusions. SLE in children is difficult to diagnose, especially in the absence of clinical polymorphism and systemic lesions. It is advisable to use the criteria proposed by EULAR and ACR, 2019, which are the most sensitive and specific in diagnosis. Treatment of patients with LN is individualized; the use of different treatment schemes depends on the severity of the pathological process. Early diagnosis of kidney damage in SLE using the criteria proposed by EULAR and ACR, 2019, and biopsy will contribute to the timely determination of the tactics and strategy of the child’s management, and improve the prognosis of Lupus nephritis. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies No conflict of interests was declared by the authors.

Biomarkers of Oxidative Stress in Systemic Lupus Erythematosus Patients with Active Nephritis.

Oxidative stress plays an important role in systemic lupus erythematosus (SLE) and especially in lupus nephritis (LN). The aim of this study was to compare redox-related biomarkers between patients with active LN, quiescent SLE (Q-SLE) and healthy controls (HC) and to explore their association with clinical characteristics such as disease activity in patients. We investigated levels of plasma free thiols (R-SH, sulfhydryl groups), levels of soluble receptor for advanced glycation end products (sRAGE) and levels of malondialdehyde (MDA) in SLE patients with active LN (n = 23), patients with quiescent SLE (n = 47) and HC (n = 23). Data of LN patients who previously participated in Dutch lupus nephritis studies and longitudinal samples up to 36 months were analyzed. Thiol levels were lower in active LN at baseline and Q-SLE patients compared to HC. In generalized estimating equation (GEE) modelling, free thiol levels were negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) over time (p < 0.001). sRAGE and MDA were positively correlated with the SLEDAI over time (p = 0.035 and p = 0.016, respectively). These results indicate that oxidative stress levels in LN patients are increased compared to HC and associated with SLE disease activity. Therefore, interventional therapy to restore redox homeostasis may be useful as an adjunctive therapy in the treatment of oxidative damage in SLE.

Platelets are a major player and represent a therapeutic opportunity in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune dysregulation and organ injury with a premature mortality due to cardiovascular diseases. Platelets, that are primarily known for their role in hemostasis, have been shown to play an active role in the pathogenesis and in the progression of immune-mediated inflammatory diseases. Here we summarize the evidence of their roles in SLE pathogenesis which supports the development of targeted treatments. Platelets and their precursors, the megakaryocytes, are intrinsically different in SLE patients compared with healthy controls. Different triggers related to innate and adaptive immunity activate platelets which release extracellular vesicles, soluble factors and interact with immune cells, thereby perpetuating inflammation. Platelets are involved in organ damage in SLE, especially in lupus nephritis and participate in the heightened cardiovascular mortality. They also play a clear role in antiphospholipid syndrome which can be associated with both thrombocytopenia and thrombosis. To tackle platelet activation and their interactions with immune cells now constitute promising therapeutic strategies in SLE.

Clinical research progress of novel biologics for the treatment of lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the loss of immune tolerance. Lupus nephritis (LN) is one of the most common manifestations of severe organ damage in SLE, and also an important cause of disability and death. Its pathogenesis is associated with immune abnormalities such as immune cells, cytokines, and immune complex deposition. Traditional immunosuppressive therapy has been unable to meet the treatment needs of patients while bringing them toxic effects. In recent years, targeted therapies have emerged, and several novel biologics have gradually entered people's sight. This review will briefly introduce the pathogenesis of LN and the mechanism of biological targets, and summarize and analyze the clinical trials of new biologics for treating LN. Although not all biologics show positive results in clinical trials, the experience learned from these trials can help researchers adjust and plan future trial programs to seek better treatment methods.

Cost-related prescription non-adherence and patient-reported outcomes in systemic lupus erythematosus: The Michigan Lupus Epidemiology & Surveillance program.

Medication access and adherence play key roles in determining patient outcomes. We investigated whether cost-related non-adherence (CRNA) to prescription medications was associated with worse patient-reported outcomes in a population-based systemic lupus erythematosus (SLE) cohort. Sociodemographic and prescription data were collected by structured interviews in 2014-2015 from patients meeting SLE criteria in the established Michigan Lupus Epidemiology & Surveillance (MILES) Cohort. We examined the associations between CRNA and potential confounders such as sociodemographics and health insurance coverage, and outcome measures of SLE activity and damage using multivariable linear regression. 462 SLE participants completed the study visit: 430 (93.1%) female, 208 (45%) Black, and mean age 53.3years. 100 (21.6%) participants with SLE reported CRNA in the preceding 12months. After adjusting for covariates, CRNA was associated with both higher levels of current SLE disease activity [SLAQ: β coeff 2.7 (95% CI 1.3, 4.1), p < 0.001] and damage [LDIQ β coeff 1.4 (95% CI 0.5, 2.4), p = 0.003]. Race, health insurance status, and fulfilling Fibromyalgia (FM) Survey Criteria were independently associated with both higher (worse) SLAQ and LDIQ scores; female sex was further associated with higher SLAQ scores. Patients with SLE who reported CRNA in the previous 12months had significantly worse self-reported current disease activity and damage scores compared to those not reporting CRNA. Raising awareness and addressing barriers or concerns related to financial implications and accessibility issues in care plans may help to improve these outcomes.

Post-COVID-19 depression and anxiety in patients with systemic lupus erythematosus.

This study aimed to evaluate depression and anxiety in patients with systemic lupus erythematosus (SLE) in the post-coronavirus disease-2019 (COVID-19) period and their potential association with the disease activity and related organ damage. This is a case-control study including 120 adult Egyptian patients with SLE: sixty patients with SLE who were proven previously to be positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) and recovered during the 3months prior to the study were included in the case group and an equal number of age- and sex-matched patients with SLE and no evidence of SARS-CoV-2 infection were included in the control group. Patients' clinical history was collected, and they underwent clinical evaluation, including SLE disease activity, damage assessment, and psychological assessment. The mean depression and anxiety scores were significantly higher in cases than in the control group. Both scores showed a significant positive correlation with age, disease duration, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for SLE (SDI), and SLE disease activity index (SLEDAI) and a significant negative correlation with education years. Hierarchical multivariate regression analyses revealed that COVID-19 infection was a predictor for severe depression and moderate-to-severe anxiety. Patients with SLE, who are already vulnerable to physiological stressors, are especially predisposed to more risk of anxiety and depression when they are contracted with COVID-19 disease. Furthermore, anxiety and depression are associated with SLE activity and damage scores, and COVID-19 infection is a significant predictor for their severity. These results suggest that healthcare providers should give special attention to the mental health of SLE patients, especially during the COVID-19 pandemic.

PREDICTION OF ATHEROSCLEROSIS DEVELOPMENT AND MODIFICATION OF ITS RISK FACTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: Early-onset atherosclerosis with cardiovascular (CV) sequelae is the major cause of death in systemic lupus erythematosus (SLE); that cannot be explained only by traditional Framingham risk factors as SLE-related factors may also have an impact. The present study aimed to analyze the determinants of atherosclerosis development and risk factors modification by statin therapy in SLE patients. Design and method: This prospective randomized study included 100 SLE patients aged 40.9±1.4 years (90 females, 10 males) and 32 age-, sex-matched healthy controls. Brachial artery flow-mediated dilation (FMD), ultrasound of extracranial and peripheral arteries, and cardiac calcium scoring were used for the identification of atherosclerosis. 52 SLE patients with dyslipidemia were randomized to receive simvastatin 40 mg/day (n = 27) or placebo (n = 25). Lipid panel, FMD, and inflammatory markers were assessed at baseline and after 6 months. Results: The mean duration of SLE was 9.9±0.88 years. The disease activity index (SLEDAI) and SLE damage score (SLICC) were 11.8±0.6 and 1.85±0.13 points, respectively. In 66% of SLE patients, atherosclerosis was present in at least one vascular area which was 3.5 times more frequently compared with controls. Atherosclerosis of carotid arteries was detected in 41% of SLE patients, lower limb arteries, and coronary arteries in 58% and 39% of patients, respectively. FMD was significantly decreased in SLE patients compared to controls (7.95±0.49% vs 11.6±0.3%, p&lt;0.001). In multiple linear regression, age (p&lt;0.001), nephritis (p = 0.001), polyarthritis (p = 0.019), and Raynaud's syndrome (p = 0.045) were associated with low FMD. In binary logistic regression, independent determinants of the atherosclerosis development in SLE were age (p&lt;0.001), body mass index (BMI) (p = 0.001), anti-dsDNA (p = 0.023), FMD (p = 0.017) and malar rash (p = 0.02). After simvastatin treatment, the level of LDL-Cholesterol reduced by 42%, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 decreased by 34.7%, 51.1%, and 47.7% respectively, while FMD increased by 26.0% (p&lt;0.05); in the placebo group, there were no significant changes. Conclusions: The independent determinants of atherosclerosis in SLE patients were both traditional CV risk factors (age, BMI) and SLE-specific factors (anti-dsDNA, malar rash, FMD). In SLE patients with dyslipidemia, simvastatin may have not only lipid-lowering but also potentially anti-inflammatory benefits.