Innate immune mechanisms are necessary for the aberrant adaptive immune responses in sle. Lupus is a systemic autoimmune disease that occurs when your bodys immune system attacks your own tissues and organs. Our objective was to update the eular recommendations for the management of systemic lupus erythematosus sle, based on emerging new evidence. Systemic lupus erythematosus university of louisville. Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li, masayuki mizui,3 and george c. Systemic lupus erythematosus larissa lisnevskaia, grainne murphy, david isenberg systemic lupus erythematosus is a remarkable and challenging disorder. Lupus, technically known as systemic lupus erythematosus sle, is an autoimmune disease in which the bodys immune system mistakenly attacks healthy tissue in many parts of the body. It is more common in african americans and people of american indian and asian descent than in. Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of sle.
The pathogenesis is multifactorial with evidence of genetic susceptibility, environmental triggers, and aberrancy in both the innate and adaptive immune systems. In this disease, the immune system of the body mistakenly attacks healthy tissue. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated. Systemic lupus erythematosus an overview sciencedirect. Pathogenesis of human systemic lupus erythematosus cell press. Systemic lupus erythematosus sle is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. Approximately 4070% of patients with sle will develop lupus nephritis.
Systemic lupus erythematosus sle is an autoimmune disease characterized by complex immunological pathogenesis and diverse clinical features, as a consequence of multisystem inflammation. Although both men and women of all age groups can be affected, women outnumber men almost 10 fold and. Jan 16, 2020 t cell subsets are critically involved in the development of systemic autoimmunity and organ inflammation in systemic lupus erythematosus sle. Crow key points systemic lupus erythematosus sle results from chronic and recurrent activation of the immune system, with production of antibodies and other protein products contributing to inflammation and tissue damage. Tcell signaling alteration in systemic lupus erythematosus sle. Influence of functional interleukin 10tumor necrosis factoralpha polymorphisms on interferonalpha, il10, and regulatory t cell population in patients with systemic lupus.
More than 90% of cases of sle occur in women, frequently starting at childbearing age. Systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. The disease has a waxing and waning course and carries significant. We discuss the role of pathological factors in the development of skin damage in sle. Sunlightinduced pathogenesis in systemic lupus erythematosus systemic lupus erythematosus sle is an extremely heter ogen eous disorder which produces a broad spectrum of ill ness in patients. What is the pathogenesis of systemic lupus erythematosus. However, research using various mouse strains of spontaneous and inducible. Most people suffering from systemic lupus erythematosus will develop pain in their muscles, joints and peripheral joints such as joints. Systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. Pathogenesis of systemic lupus erythematosus journal of.
Systemic lupus erythematosus sle is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. Systemic lupus erythematosus has many guises, but the unifying feature is the presence of antibodies against doublestranded dna in almost all patients. The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Renal assault during sle is initiated by genes that breach immune. Although accreditation for this cecme activity has expired, and the posttest is no longer available, you can still read the full article. Timely detection of sle is important, because prompt treatment can prevent its many major complicationsnotably, end organ damage. There is much interest in biomarkers, but diagnostic and. It can be life threatening when major organs are involved. Thus, testing of biomarkers against these criteria is an important area for future research. Tnfr1 and ifnifnr play an important role in the skin injury. Review pathogenesis of systemic lupus erythematosus. Pathogenesis of systemic lupus erythematosus journal of clinical.
Progranulin pgrn is an immunomodulatory protein that is upregulated in sle patients. Genetics and pathogenesis of systemic lupus erythematosus. A candidate source of autoantigen is the neutrophil extracellular trap net, which releases nucleic acids into the extracellular environment, generating a structure composed of dna coated with. Sunlightinduced pathogenesis in systemic lupus erythematosus. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli. The second most common clinical expression in lupus patients is skin damage that the pathogenesis remains unclear. Expires july 31, 2017 systemic lupus erythematosus sle is a chronic autoimmune disease that often goes undiagnosed initially.
A variety of immunological defects contribute to sle, including dysregulated innate and adaptive immune response. Aberrant innate immune responses play a significant role in the pathogenesis of sle. Overview of the pathogenesis of systemic lupus erythematosus. Aug 15, 2016 systemic lupus erythematosus, the most common form of lupus, is a chronic autoimmune disease that can cause severe fatigue and joint pain. Interplay of cytokines and chemokines in the pathogenesis of systemic lupus erythematosus. Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major role in disease activity and progression. Lie systemic lupus erythematosus sle is an auto immune disease characterized by immune dysregula tion that results in the production of autoantibodies. Systemic lupus erythematosus sle, lupus is characterized by a. Clinical and laboratory findings in seventeen patients. Immunological pathogenesis and treatment of systemic lupus. Erythematosus pathogenesis of systemic lupus and their.
In this seminar we reflect on changes in its classification criteria. Systemic lupus erythematosus sle is a chronic autoimmune disease with a broad spectrum of clinical presentations and manifestations that can affect virtually any organ or tissue of the body. Skin deposited igg is a crucial pathologic factor in the development of skin damage in sle. The interaction of sex, hormonal milieu, and the hypothalamopituitaryadrenal axis modifies this susceptibility and the clinical. Introduction systemic lupus erythematosus sle is a chronic autoimmune disease of unknown cause that can affect virtually any organ of the body. The source of autoantigen that drives disease onset and progression is unclear. The condition is much more than a positive antinuclear antibody ana. Symptoms vary between people and may be mild to severe. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. What is the pathogenesis of systemic lupus erythematosus sle.
Mar 31, 2015 systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. It can affect the skin, joints, kidneys, brain, and other. Cellular and molecular pathogenesis of systemic lupus. The exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Systemic lupus erythematosus in patients with chronic cutaneous discoid lupus erythematosus. Systemic lupus erythematosus sle is a chronic autoimmune disease affecting multiple organs. Systemic lupus erythematosus genetics home reference nih. While systemic lupus can affect any area of the body, most people experience symptoms in only a few organs. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli cated and challenging disease to diagnose and treat. Immunologic abnormalities, genetic factors, viruses, and environmental stimuli have been thought to con. As autoantibodies are critical for the pathogenesis of sle and resultant tissue injury, b cell depletion is an attractive therapeutic option in disease.
Pathogenesis of human systemic lupus erythematosus. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved sle. Apr 25, 2014 systemic lupus erythematosus sle is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Vyse, in genomic and personalized medicine second edition, 20. Pathogenesis of systemic lupus erythematosus c c mok, c s lau j clin pathol2003. Etiology and pathogenesis of systemic lupus erythematosus. Immune system exposure to excessive amounts of autoantigens that are not efficiently removed is reported to play a significant role in the generation of autoantibodies and the pathogenesis of sle. Most people suffering from systemic lupus erythematosus will develop pain in their muscles, joints and peripheral joints such as joints in their hands and knees can often become inflamed. It is more common in african americans and people of american indian and asian descent than in white people. Pathogenesis 20 and clinical features 1 introduction systemic lupus erythematosus sle is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. Pediatric systemic lupus erythematosus american academy.
Systemic lupus erythematosis sle is a complex and clinically heterogeneous autoimmune disease. Importantly, this gd regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in. The most common issue for patients suffering from systemic lupus erythematosus is to do with their joints somers et al 2007. A plasmacytoid dendritic cellstype i interferon axis is critically implicated in the pathogenesis of systemic lupus erythematosus.
Systemic lupus erythematosus is a complex multisystem autoimmune disorder with a heterogeneous presentation and clinical course. Sep 30, 2011 systemic lupus erythematosus sle is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. Systemic lupus erythematosus is the most common form of the disease. The loss of immune tolerance, increased antigenic load, excess t cell help, defective b cell suppression, and the shifting of t helper 1. Sle is an autoimmune disease in which environmental triggers in genetically susceptible individuals results in the activation of the innate and adaptive immune response, leading to a loss of tolerance to ubiquitous selfantigens. Systemic lupus erythematosus sle is a chronic, multisystem, autoimmune disease characterized by periods of increased disease activity caused by inflammation of blood vessels and connective tissue. Infections in early systemic lupus erythematosus pathogenesis. Progranulin mediates proinflammatory responses in systemic. Systemic lupus erythematosus sle, lupus is characterized by a global loss of selftolerance with activation of autoreactive t and b cells leading to production of pathogenic autoantibodies and tissue injury. The basic pathological features of sle are that of inflammation and blood vessel abnormalities, which include band or occlusive vasculopathy, vasculitis, and. The disease has a waxing and waning course and carries significant morbidity and mortality from some of its complications.
Breakdown of selftolerance is the main pathogenesis of sle. Although the term lupus erythematosus was introduced by 19thcentury physicians to describe skin lesions, it took almost 100 years to realize that the disease is systemic and spares no organ. Systemic lupus erythematosus sle is an autoimmune disease. Oct 24, 2012 systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. Systemic lupus erythematosus sle etiology likely involves complex interactions between genetic and environmental stimuli that lead to autoantibody production and chronic inflammation. Systemic lupus erythematosus sle is an immunemediated disease whose originating pathogenesis results in autoantigen exposure giving rise to numerous autoreactive antibodies of varying antigenic specificities that along with a myriad of cytokines are thought to be effectors of disease activity. Sle is a disease with typical onset in the childbearing years and most common.
Systemic lupus erythematosus overview the lupus initiative. An extremely complicated and multifactorial interaction among. The common manifestations are in the form of arthritis, skin rash, renal and hematological involvement along with fever and constitutional symptoms. There is much interest in biomarkers, but diagnostic and disease activity markers in actual clinical. College of rheumatology classification criteria for systemic lupus erythematosus.
Systemic lupus erythematosus is a systemic autoimmune disease with a worldwide distribution. Early studies in lupusprone mice revealed that b cells are absolutely essential for disease induction 48 via both autoantibodydependent. Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major. Autoimmune hepatitis was initially called chronic active hepatitis and lupoid hepatitis, and was seen in the 1960s as being akin to systemic lupus erythematosus sle by reason of shared features indicative of an autoimmune pathogenesis. Immunologic abnormalities, especially the production of a number of antinuclear antibodies ana, are a prominent feature of the disease. Systemic lupus erythematosus lupus is a chronic longlasting autoimmune disease that can affect many parts of the body. Pdf the exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Sle is a prototype type iii hypersensitivity reaction.
Nadph oxidase inhibits the pathogenesis of systemic lupus. A characteristic feature of sle is the presence of autoantibodies against doublestranded dsdna, histones and nucleosomes, and other chromatin components. We have made remarkable progress in understanding the genetics of sle over the last five years, including five published whole genome association analyses. Systemic lupus erythematosus sle is an autoimmune disease caused by the disorders of immune regulation but its pathogenesis is poorly understood.
Sle is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. Disease severity is wide ranging, with most suffering milder. Inflammation caused by lupus can affect many different body systems including your joints, skin, kidneys, blood cells, brain, heart and lungs. Multiple genes contribute to disease susceptibility. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus interactions of inflammatory cells and activated endothelium h. Pdf pathogenesis of systemic lupus erythematosus researchgate. Systemic lupus erythematosus sle is an autoimmune disease caused by cells represented in the peripheral blood circulation 57. It may affect virtually any organ or structure of the body, especially the skin, kidneys, joints, heart, gastrointestinal tract, brain, and serous membranes membranous linings of organs, joints, and cavities of the body. However, the factors involved in regulating the pathogenesis of sle by pgrn are largely unknown. Systemic lupus erythematosus sle is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course.
Systemic lupus erythematosus an overview sciencedirect topics. Pathogenesis of skin injury of systemic lupus erythematosus. The precise immunological events that trigger the onset of clinical manifestations of sle are not yet well understood. Its diversity of clinical features is matched by the complexity of the factors genetic, hormonal, and environmental that cause it, and the array of autoantibodies with which it is associated. The pathogenesis of systemic lupus erythematosus an update. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated. Systemic lupus erythematosus sle is a systemic autoimmune disease that predominantly affects the females female to male ratio is 9. The signs and symptoms of sle vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous. A diverse array of genetic factors contribute to the. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably. Genetics and pathogenesis of systemic lupus erythematosus and. Systemic lupus erythematosus sle, is the most common type of lupus. Apr 12, 2020 in systemic lupus erythematosus sle, many geneticsusceptibility factors, environmental triggers, antigenantibody ab responses, bcell and tcell interactions, and immune clearance processes. Systemic lupus erythematosus is a remarkable and challenging disorder.
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