Global epidemiology of systemic lupus erythematosus

Barber, Megan R.W.; Drenkard, Cristina; Falasinnu, Titilola; Hoi, Alberta; Mak, Anselm; Kow, Nien Yee; Svenungsson, Elisabet; Peterson, Jonna; Clarke, Ann E.; Ramsey‐Goldman, Rosalind

doi:10.1038/s41584-021-00668-1

Cited by 377 publications

(271 citation statements)

References 106 publications

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“…Production and defective elimination of antibodies, tissue deposition of immune complexes, and complement and cytokine activation contribute to clinical manifestations ranging from joint and skin inflammation to life-threatening organ damage ( 51 ). Young women are disproportionately affected by SLE with a female-to-male sex ratio around 10:1 ( 52 ). Lupus myocarditis is a rare manifestation of SLE occurring in <5% of patients ( 53 , 54 ) frequently at disease onset (≈60% of cases) ( 55 ).…”

Section: Specific Subset Of Myocarditismentioning

confidence: 99%

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

et al. 2022

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The field of inflammatory disease of the heart or “cardio-immunology” is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

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Section: Specific Subset Of Myocarditismentioning

confidence: 99%

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

et al. 2022

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“…For the comparison of the metabolite intensity between SLE and controls, we performed statistical analysis using MetaboAnalyst 5.0 (https://www.metaboanalyst.ca). Metabolites with (1) variable importance in the projection (VIP) greater than 1, (2) fold change greater than 2 or less than 0.5 and (3) P -value less than 0.05, were then log2 transformed and subjected to linear model analysis to control for confounding factors, including nutrient intake (Binary logistic regression model analysis, SPSS 24.0). For cytokine analysis, Cr was used to normalize urinary cytokine concentration.…”

Section: Methodsmentioning

confidence: 99%

“…Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a chronic relapsing-remitting course that can damage multiple organs and range from mild to life-threatening illness(1). The kidney is one of the most commonly impaired organs, and lupus nephritis (LN) has been reported in approximately 50% of SLE patients(2), 10-30% of LN patients progress to kidney failure that requires kidney replacement therapy(2), and the mortality rate within 5 years of onset directly attributed to kidney disease is 5-25% of patients with proliferative LN(2).…”

Section: Introductionmentioning

confidence: 99%

The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus

Liu

Zhai

et al. 2022

Preprint

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Background and aims: Emerging studies reveal a unique bacterial community in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. Methods and materials: We recruited a cohort of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and LC-MS/MS to perform untargeted metabolomic profiling. Results: Compared to controls, SLE patients possessed a unique bladder microbial community and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients’ disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including IL-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement C3, and Streptococcus was positively correlated with IgG. Conclusions: Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE.

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“…The cause of SLE is still unclear but genetic, environmental and hormonal factors have been linked to its predisposition. The prevalence of SLE is 366.6/100,000 in USA (2016 estimate) and 97/100,000 in UK (2012 estimate) ( Barber et al, 2021 ). Lupus Foundation of America estimates that at least five million people worldwide may have some form of lupus ( https://www.lupus.org/resources/lupus-facts-and-statistics ).…”

Section: Introductionmentioning

confidence: 99%

Targeting Regulatory T Cells for Therapy of Lupus Nephritis

et al. 2022

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Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.

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Global epidemiology of systemic lupus erythematosus

Cited by 377 publications

References 106 publications

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus

Targeting Regulatory T Cells for Therapy of Lupus Nephritis

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