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Rheumatology (Oxford, England) Dec 2020SLE is a chronic autoimmune rheumatic disorder of high heterogeneity in clinical presentation, treatment response and prognosis. Long-term outcomes in SLE have been... (Review)
Review
SLE is a chronic autoimmune rheumatic disorder of high heterogeneity in clinical presentation, treatment response and prognosis. Long-term outcomes in SLE have been dramatically improved over the past decades, however, increased morbidity and mortality, especially among young individuals, still exists. Unmet needs include residual disease activity and frequent flares, glucocorticoid treatment dependency and toxicity, comorbidity burden, reduced health-related quality of life, health disparities and damage. The main determinants of long-term outcomes in SLE are age, sex, race/ethnicity, genetic profile, environmental factors including smoking, disease activity, major organ involvement such as lupus nephritis and CNS involvement, comorbidities including cardiovascular disease and serious infections, coexistence with APS, treatment adherence, socio-economic factors and access to care. In this review we discuss trends in long-term outcomes in SLE over the years and major contributors such as genetic, disease-related, treatment, comorbidity, socio-economic and other factors.
Topics: Comorbidity; Humans; Lupus Erythematosus, Systemic; Remission Induction; Treatment Outcome
PubMed: 33280012
DOI: 10.1093/rheumatology/keaa382 -
Frontiers in Immunology 2021Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.
Topics: Adaptive Immunity; Animals; Cellular Microenvironment; Humans; Immune Tolerance; Immunity, Innate; Lupus Erythematosus, Systemic; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Phenotype; Treatment Outcome
PubMed: 34659214
DOI: 10.3389/fimmu.2021.728190 -
Journal of Autoimmunity May 2021Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality. Such outcomes impair quality of life and inflict a significant socioeconomic burden. Predicting changes in SLE disease activity could allow for closer monitoring and preemptive treatment, but existing clinical, demographic and serologic markers have been only modestly predictive. Novel, proactive approaches to clinical disease management are thus critically needed. Panels of blood biomarkers can detect a breadth of immune pathway dysregulation that captures SLE heterogeneity and disease activity. Alterations in the balance of pro-inflammatory and regulatory soluble mediators have been associated with changes in clinical disease activity and are detectable several weeks prior to clinical flare occurrence. A soluble mediator score has been highly predictive of impending flare in both European American and African American SLE patients, and this score does not require a priori knowledge of specific pathway activation in the patient. We review current concepts of disease activity and flare in SLE, focusing on the potential of novel blood biomarkers to characterize and predict changes in disease activity. Measuring the disordered immune response in SLE in this way promises to improve disease management and prevent organ damage in SLE.
Topics: Biomarkers; Cost of Illness; Cytokines; Disease Management; Disease Progression; Disease Susceptibility; Humans; Inflammation Mediators; Lupus Erythematosus, Systemic; Prevalence; Prognosis; Severity of Illness Index; Symptom Flare Up; Treatment Outcome
PubMed: 33631651
DOI: 10.1016/j.jaut.2021.102615 -
Frontiers in Immunology 2023The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were...
BACKGROUND
The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were not convincing. We aimed to investigate the relationship between SLE and hyperthyroidism or hypothyroidism by Mendelian randomization (MR) analysis.
METHODS
We performed a two-step analysis using bidirectional two-sample univariable and multivariable MR (MVMR) to explore the causality of SLE and hyperthyroidism or hypothyroidism in three genome-wide association studies (GWAS) datasets, including 402,195 samples and 39,831,813 single-nucleotide polymorphisms (SNPs). In the first step analysis, with SLE as exposure and thyroid diseases as outcomes, 38 and 37 independent SNPs strongly ( < 5*10) associated with SLE on hyperthyroidism or SLE on hypothyroidism were extracted as valid instrumental variables (IVs). In the second step analysis, with thyroid diseases as exposures and SLE as outcome, 5 and 37 independent SNPs strongly associated with hyperthyroidism on SLE or hypothyroidism on SLE were extracted as valid IVs. In addition, MVMR analysis was performed in the second step analysis to eliminate the interference of SNPs that were strongly associated with both hyperthyroidism and hypothyroidism. 2 and 35 valid IVs for hyperthyroidism on SLE and hypothyroidism on SLE were obtained in MVMR analysis. MR results of two steps analysis were estimated respectively by multiplicative random effects-inverse variance weighted (MRE-IVW), simple mode (SM), weighted median (WME) and MR-Egger regression methods. Sensitivity analysis and visualization of MR results were performed by heterogeneity test, pleiotropy test, leave-one-out test, scatter plots, forest plots and funnel plots.
RESULTS
The MRE-IVW method in the first step of MR analysis revealed that SLE was causally associated with hypothyroidism (OR = 1.049, 95% CI = 1.020-1.079, < 0.001), but not causally associated with hyperthyroidism (OR = 1.045, 95% CI = 0.987-1.107, = 0.130). In the inverse MR analysis, the MRE-IVW method revealed that both hyperthyroidism (OR = 1.920, 95% CI = 1.310-2.814, < 0.001) and hypothyroidism (OR = 1.630, 95% CI = 1.125-2.362, = 0.010) were causally associated with SLE. Results from other MR methods were consistent with MRE-IVW. However, when MVMR analysis was performed, there was no longer a causal relationship of hyperthyroidism on SLE (OR = 1.395, 95% CI = 0.984-1.978, = 0.061), nor was there a causal relationship of hypothyroidism on SLE (OR = 1.290, 95% CI = 0.823-2.022, = 0.266). The stability and reliability of the results were confirmed by sensitivity analysis and visualization.
CONCLUSIONS
Our univariable and multivariable MR analysis revealed that systemic lupus erythematosus was causally associated with hypothyroidism, but did not provided evidence to support a causal relationship of hypothyroidism on SLE or between SLE and hyperthyroidism.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Hypothyroidism; Lupus Erythematosus, Systemic
PubMed: 36860870
DOI: 10.3389/fimmu.2023.1125415 -
Frontiers in Immunology 2020The high-mobility group box 1 (HMGB1) has been shown to exert proinflammatory effects on many cells of the innate immune system. Originally identified as a nuclear... (Review)
Review
The high-mobility group box 1 (HMGB1) has been shown to exert proinflammatory effects on many cells of the innate immune system. Originally identified as a nuclear protein, HMGB1 has been found to play an important role in mediating inflammation when released from apoptotic or necrotic cells as a damage-associated molecular pattern (DAMP). Systemic lupus erythematosus (SLE) is a disease of non-resolving inflammation, characterized by the presence of autoantibodies and systemic inflammation involving multiple organ systems. SLE patients have impaired clearance of apoptotic debris, which releases HMGB1 and other DAMPs extracellularly. HMGB1 activity is implicated in multiple disease phenotypes in SLE, including lupus nephritis and neuropsychiatric lupus. Elucidating the various properties of HMGB1 in SLE provides a better understanding of the disease and opens up new opportunities for designing potential therapeutics.
Topics: Adaptive Immunity; HMGB1 Protein; Humans; Immunity, Innate; Lupus Erythematosus, Systemic; Lupus Nephritis; Lupus Vasculitis, Central Nervous System; Models, Immunological
PubMed: 32536928
DOI: 10.3389/fimmu.2020.01057 -
Current Rheumatology Reports Jan 2021To summarize current knowledge of the impact of coronavirus disease 19 (COVID-19) on patients with systemic lupus erythematosus (SLE). (Review)
Review
PURPOSE OF REVIEW
To summarize current knowledge of the impact of coronavirus disease 19 (COVID-19) on patients with systemic lupus erythematosus (SLE).
RECENT FINDINGS
Several observational studies, including case series, patient surveys, and patient registries, have examined the incidence and severity of COVID-19 in patients with SLE. Due to methodologic limitations (focus on sicker patients, exclusion of asymptomatic or mild cases, limited or inaccurate viral testing), it is difficult to determine the risk and outcomes of COVID-19 in SLE patients. Corticosteroids might be associated with increased hospitalizations from COVID-19 in individuals with autoimmune rheumatic diseases. Some immune suppressive treatments do not appear to significantly increase the risk of contracting COVID-19 or poor subsequent outcomes; however, data on the safety of specific drugs remain scarce. Studies in non-autoimmune cohorts have shown more severe COVID-19 in ethnic and racial minorities, populations also more heavily impacted by SLE. Such results have been attributed to highly prevalent socioeconomic disparities and comorbidities. The complex interplay between SARS-CoV-2 and the host immunologic milieu may have particular implications for patients with SLE that remain to be explored. Concerns have been raised of COVID-19 heightening the risk of thromboembolic events in the presence of an SLE-induced procoagulant state. Limitations in epidemiologic data available to date do not allow for assessing the risk and severity of COVID-19 in patients with SLE. Other than corticosteroids, prior use of some immune suppressive medications does not appear to increase the risk for infection with SARS-CoV-2 however, more comprehensive studies are needed.
Topics: Adrenal Cortex Hormones; Antirheumatic Agents; COVID-19; Humans; Lupus Erythematosus, Systemic
PubMed: 33511495
DOI: 10.1007/s11926-020-00973-w -
Arquivos Brasileiros de Oftalmologia 2021Lupus retinopathy is a clinical manifestation of systemic lupus erythematosus in the visual system. It is generally asymptomatic; however, it can become a threatening... (Review)
Review
Lupus retinopathy is a clinical manifestation of systemic lupus erythematosus in the visual system. It is generally asymptomatic; however, it can become a threatening condition. It is closely associated with the inflammatory activity and higher mortality of systemic lupus erythematosus. Lupus retinopathy has several different clinical presentations, such as lupus microangiopathy, vascular occlusion, vasculitis, hypertensive retinopathy associated with lupus nephritis, and autoimmune retinopathy. Although the prevalence and associated factors of lupus retinopathy have been well defined in some parts of the world, there are no data from Latin America, including Brazil. As lupus retinopathy is generally asymptomatic, without a routine fundoscopy, it has been probably underestimated. This review is intended to discuss the epidemiology and risk factors of lupus retinopathy.
Topics: Humans; Latin America; Lupus Erythematosus, Systemic; Lupus Nephritis; Retinal Diseases; Risk Factors
PubMed: 34287516
DOI: 10.5935/0004-2749.20210076 -
Chinese Medical Journal Sep 2020Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions... (Review)
Review
Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions and challenges in SLE always prompt further exploration. In 2019, great progress in various aspects of SLE emerged. Both the classification criteria and management recommendation for SLE were updated. New promising medications have been widely developed and tested, although subsequent clinical studies are warranted. As an emerging number of most notable studies in SLE were published in both clinical area and basic research in 2019, we aim to summarize the highest quality data on SLE regarding novel insights of pathogenesis, updated recommendations, hot-spot issues on clinical manifestations, new understanding of disease prognosis, and most importantly, the therapeutic advances in SLE in this review.
Topics: Autoimmune Diseases; Humans; Lupus Erythematosus, Systemic; Prognosis
PubMed: 32810049
DOI: 10.1097/CM9.0000000000000983 -
Cells Sep 2019Systemic lupus erythematosus (SLE) is a devastating and heterogeneous autoimmune disease that affects multiple organs, and for which the underlying causes are unknown.... (Review)
Review
Systemic lupus erythematosus (SLE) is a devastating and heterogeneous autoimmune disease that affects multiple organs, and for which the underlying causes are unknown. The majority of SLE patients produce autoantibodies, have increased levels of type-I inflammatory cytokines, and can develop glomerulonephritis. Recent studies indicate an unexpected but strong association between increased disease activity in SLE patients and the expression of the DNA-binding protein ARID3a (A + T rich interaction domain protein 3a) in a number of peripheral blood cell types. ARID3a expression was first associated with autoantibody production in B cells; however, more recent findings also indicate associations with expression of the inflammatory cytokine interferon alpha in SLE plasmacytoid dendritic cells and low-density neutrophils. In addition, ARID3a is expressed in hematopoietic stem cells and some adult kidney progenitor cells. SLE cells expressing enhanced ARID3a levels show differential gene expression patterns compared with homologous healthy control cells, identifying new pathways potentially regulated by ARID3a. The associations of ARID3a expression with increased disease severity in SLE, suggest that it, or its downstream targets, may provide new therapeutic targets for SLE.
Topics: Adult; Adult Stem Cells; B-Lymphocytes; DNA-Binding Proteins; Dendritic Cells; Humans; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Transcription Factors
PubMed: 31554207
DOI: 10.3390/cells8101136 -
Clinical and Experimental Rheumatology May 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. SLE pathogenesis is the... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. SLE pathogenesis is the result of complex interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal and environmental factors, and several aspects of these multifactorial connections are still unclear. Overall, for the disease development, an environmental trigger may induce immunological dysfunction in genetically predisposed individuals. This review aims to summarise the most relevant data on the impact of environmental factors on the incidence of SLE and on disease activity and damage in patients with an established diagnosis of SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Risk Factors; Gene-Environment Interaction; Genetic Predisposition to Disease; Incidence; Environmental Exposure; Environment
PubMed: 38743446
DOI: 10.55563/clinexprheumatol/17vmqc