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Annals of the Rheumatic Diseases Aug 2023Research elucidating the pathogenesis of systemic lupus erythematosus (SLE) has defined two critical families of mediators, type I interferon (IFN-I) and autoantibodies... (Review)
Review
Research elucidating the pathogenesis of systemic lupus erythematosus (SLE) has defined two critical families of mediators, type I interferon (IFN-I) and autoantibodies targeting nucleic acids and nucleic acid-binding proteins, as fundamental contributors to the disease. On the fertile background of significant genetic risk, a triggering stimulus, perhaps microbial, induces IFN-I, autoantibody production or most likely both. When innate and adaptive immune system cells are engaged and collaborate in the autoimmune response, clinical SLE can develop. This review describes recent data from genetic analyses of patients with SLE, along with current studies of innate and adaptive immune function that contribute to sustained IFN-I pathway activation, immune activation and autoantibody production, generation of inflammatory mediators and tissue damage. The goal of these studies is to understand disease mechanisms, identify therapeutic targets and stimulate development of therapeutics that can achieve improved outcomes for patients.
Topics: Humans; Lupus Erythematosus, Systemic; Autoantibodies; Interferon Type I
PubMed: 36792346
DOI: 10.1136/ard-2022-223741 -
JAMA May 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the... (Review)
Review
IMPORTANCE
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems. Approximately 3.4 million people worldwide have received a diagnosis of SLE.
OBSERVATIONS
Approximately 90% of people with SLE are female. Although there are no uniformly accepted diagnostic criteria for SLE, the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE. These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis; and immunologic measures, such as SLE-specific autoantibodies and low complement levels. Approximately 40% of people with SLE develop lupus nephritis, and an estimated 10% of people with lupus nephritis develop end-stage kidney disease after 10 years. The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications. Treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity. Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality. Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease. Three SLE medications were recently approved by the Food and Drug Administration: belimumab (for active SLE in 2011 and for lupus nephritis in 2020), voclosporin (for lupus nephritis), and anifrolumab (for active SLE).
CONCLUSIONS AND RELEVANCE
Systemic lupus erythematosus is associated with immune-mediated damage to multiple organs and increased mortality. Hydroxychloroquine is first-line therapy and reduces disease activity, morbidity, and mortality. When needed, additional immunosuppressive and biologic therapies include azathioprine, mycophenolate mofetil, cyclophosphamide, belimumab, voclosporin, and anifrolumab.
Topics: Female; Humans; Male; Autoantibodies; Biological Products; Black or African American; Hydroxychloroquine; Immunomodulating Agents; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Race Factors; Sex Factors; White
PubMed: 38587826
DOI: 10.1001/jama.2024.2315 -
Archives of Gynecology and Obstetrics Jul 2023Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the... (Review)
Review
Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Lupus Erythematosus, Systemic; Symptom Flare Up; Pregnancy Outcome; Pregnancy Complications; Antibodies, Antiphospholipid
PubMed: 35913558
DOI: 10.1007/s00404-022-06718-7 -
BMJ (Clinical Research Ed.) Oct 2023Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of... (Review)
Review
Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that can cause injury in almost every body system. While considered a classic example of autoimmunity, it is still relatively poorly understood. Treatment with immunosuppressive agents is challenging, as many agents are relatively non-specific, and the underlying disease is characterized by unpredictable flares and remissions. This State of The Art Review provides a comprehensive current summary of systemic lupus erythematosus based on recent literature. In basic and translational science, this summary includes the current state of genetics, epigenetics, differences by ancestry, and updates about the molecular and immunological pathogenesis of systemic lupus erythematosus. In clinical science, the summary includes updates in diagnosis and classification, clinical features and subphenotypes, and current guidelines and strategies for treatment. The paper also provides a comprehensive review of the large number of recent clinical trials in systemic lupus erythematosus. Current knowns and unknowns are presented, and potential directions for the future are suggested. Improved knowledge of immunological pathogenesis and the molecular differences that exist between patients should help to personalize treatment, minimize side effects, and achieve better outcomes in this difficult disease.
Topics: Humans; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Autoimmunity
PubMed: 37884289
DOI: 10.1136/bmj-2022-073980 -
Lancet (London, England) May 2024Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex... (Review)
Review
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys. Despite substantial advances in the diagnosis and management of SLE, the burden of disease remains high. It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients. In most patients, constitutional, mucocutaneous, and musculoskeletal symptoms represent the earliest complaints; these symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia. In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria, which include a systematic evaluation of clinical manifestations (weighted within each domain) and autoantibody profiles (such as anti-double-stranded DNA, anti-Sm, hypocomplementaemia, or antiphospholipid antibodies). Non-pharmacotherapy management is tailored to the individual, with specific lifestyle interventions and patient education to improve quality of life and medication (such as hydroxychloroquine or immunosuppressant) adherence. In the last decade, there have been a few major breakthroughs in approved treatments for SLE and lupus nephritis, such as belimumab, anifrolumab, and voclosporin. However the disease course remains variable and mortality unacceptably high. Access to these expensive medications has also been restricted across different regions of the world. Nonetheless, understanding of treatment goals and strategies has improved. We recognise that the main goal of treatment is the achievement of remission or low disease activity. Comorbidities due to both disease activity and treatment adverse effects, especially infections, osteoporosis, and cardiovascular disease, necessitate vigilant prevention and management strategies. Tailoring treatment options to achieve remission, while balancing treatment-related comorbidities, are priority areas of SLE management.
Topics: Humans; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Autoantibodies
PubMed: 38642569
DOI: 10.1016/S0140-6736(24)00398-2 -
Nature Reviews. Rheumatology Mar 2024Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue... (Review)
Review
Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone.
Topics: Humans; Sjogren's Syndrome; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Autoimmune Diseases; Scleroderma, Systemic
PubMed: 38110617
DOI: 10.1038/s41584-023-01057-6 -
Intensive Care Medicine Jan 2024Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting... (Review)
Review
Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.
Topics: Humans; Autoimmune Diseases; Lupus Erythematosus, Systemic; Intensive Care Units; Vasculitis; Autoantibodies
PubMed: 38112769
DOI: 10.1007/s00134-023-07266-7 -
Revista Clinica Espanola Dec 2023Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as... (Review)
Review
Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials.
Topics: Humans; Quality of Life; Lupus Erythematosus, Systemic; Prognosis; Biological Therapy; Immunosuppressive Agents
PubMed: 38000622
DOI: 10.1016/j.rceng.2023.11.001 -
Nature Reviews. Nephrology Aug 2023Kidney involvement in patients with systemic lupus erythematosus - lupus nephritis (LN) - is one of the most important and common clinical manifestations of this disease... (Review)
Review
Kidney involvement in patients with systemic lupus erythematosus - lupus nephritis (LN) - is one of the most important and common clinical manifestations of this disease and occurs in 40-60% of patients. Current treatment regimens achieve a complete kidney response in only a minority of affected individuals, and 10-15% of patients with LN develop kidney failure, with its attendant morbidity and considerable prognostic implications. Moreover, the medications most often used to treat LN - corticosteroids in combination with immunosuppressive or cytotoxic drugs - are associated with substantial side effects. Advances in proteomics, flow cytometry and RNA sequencing have led to important new insights into immune cells, molecules and mechanistic pathways that are instrumental in the pathogenesis of LN. These insights, together with a renewed focus on the study of human LN kidney tissue, suggest new therapeutic targets that are already being tested in lupus animal models and early-phase clinical trials and, as such, are hoped to eventually lead to meaningful improvements in the care of patients with systemic lupus erythematosus-associated kidney disease.
Topics: Animals; Humans; Lupus Nephritis; Lupus Erythematosus, Systemic; Kidney; Immunosuppressive Agents; Adrenal Cortex Hormones
PubMed: 37225921
DOI: 10.1038/s41581-023-00722-z -
Current Rheumatology Reports Oct 2023To describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake,... (Review)
Review
PURPOSE OF REVIEW
To describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake, immunogenicity and safety, and (ii) outcomes of COVID-19 in patients with SLE and pertinent risk factors for adverse sequelae.
RECENT FINDINGS
Notwithstanding the potential concern of patients about possible post-vaccination side-effects, the safety of anti-SARS-CoV-2 vaccines in patients with SLE has been undisputedly confirmed in numerous studies. Humoral immunogenicity is generally attained in SLE, although affected by the use of background immunosuppressive drugs, especially rituximab. The latter has also clearly been implicated with adverse COVID-19 outcomes in SLE, including need for hospitalization, mechanical ventilation and death. Although the wide adoption of vaccination has significantly improved COVID-19 outcomes, patients with SLE continue to pose challenges during the pandemic, mainly owing to administered immunosuppressive medications.
Topics: Humans; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Lupus Erythematosus, Systemic; Immunosuppressive Agents
PubMed: 37477841
DOI: 10.1007/s11926-023-01110-z