Immunological pathogenesis and treatment of systemic lupus. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli cated and challenging disease to diagnose and treat. Systemic autoimmunity in systemic lupus erythematosus. Mar 31, 2015 systemic lupus erythematosus sle is a complex, autoimmune disorder that can have debilitating effects on various organs, including the kidneys. Lupus nephritis ln is a common and severe organ manifestation of systemic lupus erythematosus sle, and is associated with significant patient morbidity and mortality. Pathogenesis of human systemic lupus erythematosus cell press. 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. Systemic lupus erythematosus, pathogenesis request pdf. Cytokines and their roles in the pathogenesis of systemic. Systemic lupus erythematosus sle is an autoimmune disease that impacts many body systems, with a wide variety of signs and symptoms in each patient. Systemic lupus erythematosus sle is an autoimmune disease with an extremely complex pathogenesis. 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.
Patients with systemic lupus erythematosus sle may experience malar rash, arthritis, renal damage, and a wide range of other clinical manifestations with the potential to affect any organ system. Research efforts of the last few years have mainly focused on basic molecular and cellular pathogenetic processes of the. What is the pathogenesis of systemic lupus erythematosus sle updated. Read an overview of the pathophysiology of systemic lupus.
What is the pathogenesis of systemic lupus erythematosus. Sle is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. Pathogenesis of human systemic lupus erythematosus. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of sle and ln, and might reflect disease activity and are amenable to. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated. Micrornasnovel regulators of systemic lupus erythematosus pathogenesis. Clinical manifestations and diagnosis of systemic lupus.
Systemic lupus erythematosus sle is a heterogeneous autoimmune disorder characterized by the presence of pathogenic autoantibodies, immune complex formation and deposition in various organs, profound innate and adaptive immune dysregulation and inflammation, and a wide range of clinical manifestations including kidney involvement 1, 2. Systemic lupus erythematosus is a remarkable and challenging disorder. Systemic lupus erythematosus sle is an autoimmune disease. The exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Review pathogenesis of systemic lupus erythematosus. 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. Genomewide association studies gwas have progressively improved understanding of which genes are most. Systemic lupus erythematosis sle is a complex and clinically heterogeneous autoimmune disease. Etiology and pathogenesis of systemic lupus erythematosus. 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. Pathogenesis of systemic lupus erythematosus sle studies have focused on the role of adaptive immunity, however recent findings show multiple elements of the immune system in systemic lupus erythematosus.
Systemic lupus erythematosus sle is an autoimmune disease characterized by complex immunological pathogenesis and diverse clinical features, as a consequence of multisystem inflammation. Sle is characterised by a myriad of immune system aberrations that involve b cells, t cells, and cells of the monocytic lineage, resulting in polyclonal b cell. 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. Systemic lupus erythematosus sle, or lupus is a systemic autoimmune disease with multiorgan inflammation. Systemic lupus erythematosus sle is a remarkably complex and heterogeneous systemic autoimmune disease.
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 sle is a complex autoimmune disorder which involves various facets of the immune system. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. Systemic lupus erythematosus sle is an autoimmune disease in which the bodys immune system attacks its own healthy tissue. 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. Pathogenesis of systemic lupus erythematosus journal of. Epidemiology and pathogenesis of systemic lupus erythematosus uptodate the reported prevalence of systemic lupus erythematosus sle in the united states is 20 to 150 cases per 100,000. Pathogenesis of systemic lupus erythematosus request pdf. 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. Disease complexity within individuals and heterogeneity among individuals, even genetically identical individuals, is driven by stochastic execution of a complex inherited program.
It can affect the skin, joints, kidneys, brain, and other organs. Nadph oxidase inhibits the pathogenesis of systemic lupus. It is more common in african americans and people of american indian and asian descent than in white people. An extremely complicated and multifactorial interaction among.
Symptoms vary between people and may be mild to severe. Systemic lupus erythematosus is a multisystem disease of unknown etiology in which dysregulation of the innate and adaptive immune systems has a major effect in the pathogenesis of the disease. Systemic lupus erythematosus sle is a prototypic autoimmune disease characterised by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations. 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. Epigenetics in the pathogenesis of systemic lupus erythematosus. 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. Chance, genetics, and the heterogeneity of disease and. Some genes implicated in systemic lupus erythematosus sle and lupus nephritis might contribute to the pathology of disease by breaching immune tolerance and promoting autoantibody production.
Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li, masayuki mizui,3 and george c. Cellular and molecular pathogenesis of systemic lupus. In women, prevalence rates vary from 164 whi it seems to us that you. The reported prevalence of systemic lupus erythematosus sle in the united states is 20 to 150 cases per 00. Mar 18, 2020 systemic lupus erythematosus sle is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. Pathophysiology of lupus pathophysiology of sle dr. 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. Introduction systemic lupus erythematosus sle is a chronic autoimmune disease of unknown cause that can affect virtually any organ of the body. Systemic lupus erythematosus in patients with chronic cutaneous discoid lupus erythematosus. Although the pathogenesis of sle has been attributed to many factors, the detailed mechanisms remain unclear blank et al.
Metabolism as a key regulator in the pathogenesis of. Jan 16, 2020 t cell subsets are critically involved in the development of systemic autoimmunity and organ inflammation in systemic lupus erythematosus sle. Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li. The source of autoantigen that drives disease onset and progression is unclear.
Systemic lupus erythematosus sle, or lupus, is an autoimmune disease in which a persons immune system attacks various organs or cells of the body, causing damage and dysfunction. The disease has a waxing and waning course and carries significant morbidity and mortality from some of its complications. 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 a complex disease characterized by the appearance of autoantibodies against nuclear antigens and. Dissecting complex epigenetic alterations in human lupus. Multiple genes contribute to disease susceptibility. It can be life threatening when major organs are involved. See epidemiology and pathogenesis of systemic lupus erythematosus, section on epidemiology. Seek medical care for lupus if you have rapid swelling of one of your extremities. 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. Systemic lupus erythematosus sle is a chronic autoimmune disease affecting multiple organs. Systemic lupus erythematosus an overview sciencedirect.
Predominantly targeting young women in their childbearing years and with the potential to cause significant physical disfigurement, morbidity, and occasionally mortality, lupus is the focus of strong advocacy to support research that will generate insights into disease pathogenesis. New loci and genes have been associated with the expression of sle. Systemic lupus erythematosus definition systemic lupus erythematosus sle is an autoimmune disease. The pathogenesis of systemic lupus erythematosus an update. The accumulation of mitochondria is a prominent source of increased production of reactive oxygen intermediates roi in t cells. Due to a genetic predisposition the disease can be induced by multiple stress factors involving epigenetic mechanisms and under the influence of the innate immune system. As an example, the diagnosis of sle is more likely to be present in a young woman who develops fatigue, arthralgia, and pleuritic chest pain and is found to have hypertension, a malar rash, a pleural friction rub, several tender and swollen joints. Metabolic changes in autoimmune diseases might be due to inflammation as well as being involved in autoimmune pathogenesis. Systemic lupus erythematosus penn state hershey medical center. A diverse array of genetic factors contribute to the. The interaction of sex, hormonal milieu, and the hypothalamopituitaryadrenal axis modifies this susceptibility and the clinical. Systemic lupus erythematosus sle is a chronic, multisystem autoimmune disorder that can affect nearly every major organ system, causing inflammation, tissue injury, organ damage, and, ultimately, organ dysfunction. Apr 12, 2020 in systemic lupus erythematosus sle, many geneticsusceptibility factors, environmental triggers, antigenantibody ab responses, bcell and tcell interactions, and immune clearance processes.
Pdf the exact pathoaetiology of systemic lupus erythematosus sle remains elusive. 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. Genetics and pathogenesis of systemic lupus erythematosus and. Review this overview and discuss any symptoms you have with your doctor. The pathogenesis of systemic lupus erythematosus an. Although both men and women of all age groups can be affected, women outnumber men. Photosensitive systemic lupus erythematosus sle rashes typically occur on the face or extremities, which are sunexposed regions. Pathophysiology of lupus is currently being studied in all areas of the disease and many believe it could be a way to abolish the disease. What is the pathogenesis of systemic lupus erythematosus sle. More than 90% of cases of sle occur in women, frequently starting at childbearing age. Pathogenesis of systemic lupus erythematosus c c mok, c s lau j clin pathol2003. Some genes implicated in systemic lupus erythematosus sle and lupus nephritis might contribute to the pathology of disease by breaching immune tolerance and. Immunologic abnormalities, especially the production of a number of antinuclear antibodies ana, are a prominent feature of the disease.
In addition to autoantibody production and immune complex deposition, emerging evidences suggest that cytokines may act as key players in the immunopathogenesis of sle. The disease has a waxing and waning course and carries significant. Systemic lupus erythematosus genetics home reference nih. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably. The precise immunological events that trigger the onset of clinical manifestations of sle are not yet well understood. Systemic lupus erythematosus sle is a chronic autoimmune disease with a broad spectrum of clinical presentations and manifestations that can affect virtually. Whereas there is little evidence to indicate whether selfantigens in sle are aberrant in sequence or structure, there is evidence that the aberrant handling of selfantigens could facilitate lupus pathogenesis. Systemic lupus erythematosus, the most common form of lupus, is a chronic autoimmune disease that can cause severe fatigue and joint pain. Pathogenesis and clinical features 477 disease starts with a preclinical phase characterised by autoantibodies common to other systemic autoimmune diseases and proceeds with a more diseasespecifi c clinically overt autoimmune phase bertsias et al 2010a. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated. Systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids.
In this disease, the immune system of the body mistakenly attacks healthy tissue. Systemic lupus erythematosus sle is an autoimmune disease with heterogenous clinical presentations whose precise pathophysiological mechanism is largely unknown. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. Systemic lupus erythematosus sle is a disease characterized by the production of autoreactive antibodies and cytokines, which are thought to have a major. In this seminar we reflect on changes in its classification criteria. Systemic lupus erythematosus sle is a chronic, potentially fatal autoimmune disease, characterized by dysregulation of immune cells and production of autoantibodies that cause widespread tissue and organ damage. Cellular and molecular pathogenesis of systemic lupus erythematosus. A variety of immunological defects contribute to sle, including dysregulated innate and adaptive immune response. The role of autophagy in the pathogenesis of systemic. While systemic lupus can affect any area of the body, most people experience symptoms in only a few organs.
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. The causes of systemic lupus erythematosus sle are unknown. Jul 17, 2016 lupus erythematosus lupus erythematosus le may be seen in one of two wellrecognized forms systemic acute lupus erythematosus sle profound impact it has on many organs discoid chronic lupus erythematosus dle chronic and localised skin lesions involving the bridge of nose and adjacent cheeks without any. Advances in the diagnosis, pathogenesis and treatment of. The pathogenesis of systemic lupus erythematosus from. Systemic lupus erythematosus sle is a chronic autoimmune disease with varied natural history and multisystemic involvement. Epidemiology and pathogenesis of systemic lupus erythematosus. Systemic lupus erythematosus lupus is a chronic longlasting autoimmune disease that can affect many parts of the body. 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. Genetics and pathogenesis of systemic lupus erythematosus.
Pathophysiology is defined as the study the biological and physical manifestations of disease as the correlate with the underlying abnormalities and. Systemic lupus erythematosus is the most common form of the disease. It presents accumulating data for a role of epsteinbarr virus ebv in lupus initiation, followed by work in other pathogens linked with sle autoimmunity. Although the interphalangeal spaces are affected, the metacarpophalangeal mcp and proximal interphalangeal pip and. Infections in early systemic lupus erythematosus pathogenesis. 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. The pathophysiology of systemic lupus erythematosus includes the nervous system, digestion, heart, lungs, blood, muscles, bones, kidneys and skin. Systemic lupus erythematosus sle represents one of the most significant diseases in all of medicine. Pdf pathogenesis of systemic lupus erythematosus researchgate. Systemic lupus erythematosus is an autoimmune disease of unknown etiology. Clinical and laboratory findings in seventeen patients. 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.
Although both men and women of all age groups can be affected, women outnumber men almost 10 fold and. 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. Systemic lupus erythematosus sle, is the most common type of lupus. Systemic lupus erythematosus sle, a prototype of systemic autoimmune disease, is characterized by the production of pathogenic autoantibodies by dysfunctional immunocompetent cells which results in multiple organ injuries. It can affect the skin, joints, kidneys, brain, and other. A complex interaction of genetics, environment, and hormones. It is known that genetic factors, hormonal, infectious and environmental issues can have important role in its pathogenesis.
This chapter focuses on examining roles for infection in the initiation and pathogenesis of systemic lupus erythematosus sle. The pathoaetiology of systemic lupus erythematosus sle probably involves complicated and multifactorial interactions among various genetic and environmental factors multiple genes contribute to disease susceptibility, including genes encoding complement and other components of the immune response, in addition to major histocompatibility complex class i and ii genes. Systemic lupus erythematosus sle, an autoimmune disorder which primarily affects women 10. Pathophysiology of lupus pathophysiology of sle dr garys.
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