The interaction of sex, hormonal milieu, and the hypothalamopituitaryadrenal axis modifies this susceptibility and the clinical. Erythematosus pathogenesis of systemic lupus and their. Most people suffering from systemic lupus erythematosus will develop pain in their muscles, joints and peripheral joints such as joints. Systemic lupus erythematosus is a remarkable and challenging disorder. Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of sle. Systemic lupus erythematosus larissa lisnevskaia, grainne murphy, david isenberg systemic lupus erythematosus is a remarkable and challenging disorder. Systemic lupus erythematosus sle is a systemic autoimmune disease that predominantly affects the females female to male ratio is 9. 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. The source of autoantigen that drives disease onset and progression is unclear. Tnfr1 and ifnifnr play an important role in the skin injury. Aberrant innate immune responses play a significant role in the pathogenesis of sle.
It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated. Overview of the pathogenesis of systemic lupus erythematosus. The pathogenesis of systemic lupus erythematosus an update.
The exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Innate immune mechanisms are necessary for the aberrant adaptive immune responses in sle. 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. Systemic lupus erythematosus sle is an autoimmune disease caused by cells represented in the peripheral blood circulation 57. The loss of immune tolerance, increased antigenic load, excess t cell help, defective b cell suppression, and the shifting of t helper 1. Pathogenesis of human systemic lupus erythematosus cell press. A characteristic feature of sle is the presence of autoantibodies against doublestranded dsdna, histones and nucleosomes, and other chromatin components.
Vyse, in genomic and personalized medicine second edition, 20. As autoantibodies are critical for the pathogenesis of sle and resultant tissue injury, b cell depletion is an attractive therapeutic option in disease. Skin deposited igg is a crucial pathologic factor in the development of skin damage in sle. The precise immunological events that trigger the onset of clinical manifestations of sle are not yet well understood. Systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. 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. Early studies in lupusprone mice revealed that b cells are absolutely essential for disease induction 48 via both autoantibodydependent. 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. Introduction systemic lupus erythematosus sle is a chronic autoimmune disease of unknown cause that can affect virtually any organ of the body. Sle is a prototype type iii hypersensitivity reaction. Although both men and women of all age groups can be affected, women outnumber men almost 10 fold and. 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 has many guises, but the unifying feature is the presence of antibodies against doublestranded dna in almost all patients. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli cated and challenging disease to diagnose and treat.
Systemic lupus erythematosus sle, lupus is characterized by a. The pathogenesis is multifactorial with evidence of genetic susceptibility, environmental triggers, and aberrancy in both the innate and adaptive immune systems. Cellular and molecular pathogenesis of systemic lupus. Pdf the exact pathoaetiology of systemic lupus erythematosus sle remains elusive. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li, masayuki mizui,3 and george c. 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. 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. 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.
Symptoms vary between people and may be mild to severe. More than 90% of cases of sle occur in women, frequently starting at childbearing age. Apr 25, 2014 systemic lupus erythematosus sle is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Pathogenesis of skin injury of systemic lupus erythematosus. Clinical and laboratory findings in seventeen patients. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli. 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. College of rheumatology classification criteria for systemic lupus erythematosus. Interplay of cytokines and chemokines in the pathogenesis of systemic lupus erythematosus. However, the factors involved in regulating the pathogenesis of sle by pgrn are largely unknown. Lupus is a systemic autoimmune disease that occurs when your bodys immune system attacks your own tissues and organs. Expires july 31, 2017 systemic lupus erythematosus sle is a chronic autoimmune disease that often goes undiagnosed initially.
The most common issue for patients suffering from systemic lupus erythematosus is to do with their joints somers et al 2007. 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 is the most common form of the disease. Sle is a disease with typical onset in the childbearing years and most common. Our objective was to update the eular recommendations for the management of systemic lupus erythematosus sle, based on emerging new evidence.
Oct 24, 2012 systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. Pediatric systemic lupus erythematosus american academy. While systemic lupus can affect any area of the body, most people experience symptoms in only a few organs. Infections in early systemic lupus erythematosus pathogenesis. Systemic lupus erythematosus an overview sciencedirect. 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.
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. A variety of immunological defects contribute to sle, including dysregulated innate and adaptive immune response. Systemic lupus erythematosus sle is an autoimmune disease. 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.
There is much interest in biomarkers, but diagnostic and disease activity markers in actual clinical. The disease has a waxing and waning course and carries significant morbidity and mortality from some of its complications. A plasmacytoid dendritic cellstype i interferon axis is critically implicated in the 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. 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. 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. Pathogenesis of systemic lupus erythematosus journal of clinical. The second most common clinical expression in lupus patients is skin damage that the pathogenesis remains unclear. 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. In this disease, the immune system of the body mistakenly attacks healthy tissue. However, research using various mouse strains of spontaneous and inducible.
Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major. Systemic lupus erythematosus sle is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. Progranulin mediates proinflammatory responses in systemic. Systemic lupus erythematosus genetics home reference nih. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated. Thus, testing of biomarkers against these criteria is an important area for future research. Importantly, this gd regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in. Pathogenesis of systemic lupus erythematosus c c mok, c s lau j clin pathol2003. Timely detection of sle is important, because prompt treatment can prevent its many major complicationsnotably, end organ damage.
We have made remarkable progress in understanding the genetics of sle over the last five years, including five published whole genome association analyses. Mar 31, 2015 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. Pdf pathogenesis of systemic lupus erythematosus researchgate. Jan 16, 2020 t cell subsets are critically involved in the development of systemic autoimmunity and organ inflammation in systemic lupus erythematosus sle. We discuss the role of pathological factors in the development of skin damage in sle. 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. Etiology and pathogenesis of systemic lupus erythematosus. Although accreditation for this cecme activity has expired, and the posttest is no longer available, you can still read the full article. Systemic lupus erythematosus sle is an autoimmune disease characterized by complex immunological pathogenesis and diverse clinical features, as a consequence of multisystem inflammation.
Immunological pathogenesis and treatment of systemic lupus. Pathogenesis of human systemic lupus erythematosus. Systemic lupus erythematosus sle is an autoimmune disease caused by the disorders of immune regulation but its pathogenesis is poorly understood. The condition is much more than a positive antinuclear antibody ana. The disease has a waxing and waning course and carries significant. Renal assault during sle is initiated by genes that breach immune. It can affect the skin, joints, kidneys, brain, and other. Systemic lupus erythematosus sle etiology likely involves complex interactions between genetic and environmental stimuli that lead to autoantibody production and chronic inflammation. What is the pathogenesis of systemic lupus erythematosus. A diverse array of genetic factors contribute to the. An extremely complicated and multifactorial interaction among. Approximately 4070% of patients with sle will develop lupus nephritis.
What is the pathogenesis of systemic lupus erythematosus sle. Systemic lupus erythematosis sle is a complex and clinically heterogeneous autoimmune disease. Clinical presentation, pathophysiology, and therapeutic strategies over the course of disease. Pathology and pathogenesis of vascular injury in systemic lupus erythematosus interactions of inflammatory cells and activated endothelium h.
Systemic lupus erythematosus an overview sciencedirect topics. Systemic lupus erythematosus is a systemic autoimmune disease with a worldwide distribution. Immunologic abnormalities, genetic factors, viruses, and environmental stimuli have been thought to con. There is much interest in biomarkers, but diagnostic and. The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. It is more common in african americans and people of american indian and asian descent than in. 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. Systemic lupus erythematosus sle is a chronic autoimmune disease affecting multiple organs.
Review pathogenesis of systemic lupus erythematosus. Systemic lupus erythematosus overview the lupus initiative. 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. Multiple genes contribute to disease susceptibility. It is more common in african americans and people of american indian and asian descent than in white people. Sunlightinduced pathogenesis in systemic lupus erythematosus. Genetics and pathogenesis of systemic lupus erythematosus.
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. Sle is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. The basic pathological features of sle are that of inflammation and blood vessel abnormalities, which include band or occlusive vasculopathy, vasculitis, and. 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. 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. Systemic lupus erythematosus university of louisville. Systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. Systemic lupus erythematosus in patients with chronic cutaneous discoid lupus erythematosus.
In this seminar we reflect on changes in its classification criteria. Nadph oxidase inhibits the pathogenesis of systemic lupus. Progranulin pgrn is an immunomodulatory protein that is upregulated in sle patients. Immunologic abnormalities, especially the production of a number of antinuclear antibodies ana, are a prominent feature of the disease. The common manifestations are in the form of arthritis, skin rash, renal and hematological involvement along with fever and constitutional symptoms. Influence of functional interleukin 10tumor necrosis factoralpha polymorphisms on interferonalpha, il10, and regulatory t cell population in patients with systemic lupus.
1159 386 274 271 599 1643 1219 32 478 116 579 587 377 1251 1523 978 980 1677 1470 175 111 1297 51 1362 453 1237 90 941 1080 905 425 446 1057 1374 843 3 1097 1373