This book provides a comprehensive overview of the basic and clinical sciences of systemic lupus erythematosus. Sle is a polygenic disorder that can appear in individuals without a family history of the disease, yet siblings of affected individuals are much more likely to develop sle, and monozygotic twins. Systemic lupus erythematosus, pathogenesis request pdf. 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 transmitted in a polygenic inheritance pattern. The epub format uses ebook readers, which have several ease of reading features already built in. Nadph oxidase inhibits the pathogenesis of systemic lupus.
This article is from pediatric rheumatology online journal, volume 10. The pathogenesis of systemic lupus erythematosus an update. Systemic lupus erythematosus, a manual, is a useful reference for specialists in the diagnosis and management of patients with sle, a tool for measurement of clinical activity for pharmaceutical development and basic research of the disease and a reference work for hospital libraries. We have made remarkable progress in understanding the genetics of sle over the last five years, including five. Jci inhibition of shp2 ameliorates the pathogenesis of. T cell subsets are critically involved in the development of systemic autoimmunity and organ inflammation in systemic lupus erythematosus sle. Systemic lupus erythematosus sle is an autoimmune disease characterized by loss of tolerance to self nucleic acids. Safety and efficacy of metformin in systemic lupus.
Systemic lupus erythematosus pathophysiology wikidoc. Although there is no definate cause of systemic lupus erythematosus giannouli 2006, there is thought to be several factors increasing the likelihood of developing systemic lupus erythematous they include genetics where members of the family have lupus this condition will often increase the childs chances of developing it hemminki 2009. 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. Pdf the exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Systemic lupus erythematosus sle is an autoimmune inflammatory diseases attributed to genetic and environmental factors causing the dysfunction of t cells, b. Katarzyna gilekseibert, md abstract systemic lupus erythematosus sle is a chronic, compli. The source of autoantigen that drives disease onset and progression is unclear. Patients may present with a wide array of symptoms, signs, and laboratory findings and have a variable prognosis that depends upon the disease severity and type of organ involvement. Systemic lupus erythematosus is a group of diseases that seem to become separate entities by etiology in the near future. Genes involved in human systemic lupus erythematosus. 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.
From basic scientific principles to practical points of clinical management, the updated 9th edition provides extensive, authoritative coverage of systemic lupus. Multiple genetic defects, drug exposure, infectious agents, and environmental factors can contribute to the pathogenesis of the disease. Hence, inhibition of jak signals has provided an attractive therapeutic option in sle. Systemic lupus erythematosus is an autoimmune disease in which the bodys immune system mistakenly attacks healthy tissue. Genetics and pathogenesis of systemic lupus erythematosus. The disease has been studied in dogs as the animal model for sle in humans. 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. There are several kinds of lupus systemic lupus erythematosus sle is the form of the disease that most people are referring to when they say lupus. Vyse, in genomic and personalized medicine second edition, 20. Fecal microbiota from c57bl6 mice and sle prone mice were examined using nextgeneration sequencing.
Although accreditation for this cecme activity has expired, and the posttest is no longer available, you can still read the full article. The word systemic means the disease can affect many parts of the body. Systemic lupus erythematosis sle is a complex and clinically heterogeneous autoimmune disease. Disease complexity within individuals and heterogeneity among individuals, even genetically identical individuals, is driven by stochastic execution of a complex inherited program. Dubois lupus erythematosus and related syndromes has been recognized internationally as the goto clinical reference on lupus and other connective tissue diseases. Systemic lupus erythematosus sle, lupus is characterized by a. Pathogenesis of systemic lupus erythematosus c c mok, c s lau j clin pathol2003. Cellular and molecular pathogenesis of systemic lupus. Pathogenic mechanisms in systemic lupus erythematosus ncbi. Review pathogenesis of systemic lupus erythematosus. Progranulin mediates proinflammatory responses in systemic. Systemic lupus erythematosus larissa lisnevskaia, grainne murphy, david isenberg systemic lupus erythematosus is a remarkable and challenging disorder. The autoantibodies are nephritogenic, with onethird of females.
Pdf pathogenesis of systemic lupus erythematosus researchgate. 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. A variety of immunological defects contribute to sle, including dysregulated innate and adaptive immune response. Systemic lupus erythematosus an overview sciencedirect. Immunological pathogenesis and treatment of systemic lupus erythematosus. However, research using various mouse strains of spontaneous.
An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. Symptoms vary between people and may be mild to severe. Abstractthe pathogenesis of systemic lupus erythematosus sle is complex and remains. Immunometabolism is involved in the pathogenesis of systemic lupus erythematosus sle. Pdf pathogenesis of human systemic lupus erythematosus. Taming lupusa new understanding of pathogenesis is leading to clinical advances. The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. In lupus, the bodys immune system, which normally functions to protect against foreign invaders, becomes hyperactive, forming antibodies that attack normal tissues and organs, including the skin.
Janus kinases jaks are intracellular tyrosine kinases which play a key role in the signal pathways of many cytokines, such as type l interferons ifns, interleukin6 il6, il12 and il23. Influence of functional interleukin 10tumor necrosis factoralpha polymorphisms on interferonalpha, il10, and regulatory t cell population in patients with systemic lupus. Systemic lupus erythematosus sle is an autoimmune disease caused by the disorders of immune regulation but its pathogenesis is poorly understood. The interaction of sex, hormonal milieu, and the hypothalamopituitaryadrenal axis modifies this susceptibility and the clinical. Pathogenesis of human systemic lupus erythematosus. Dubois lupus erythematosus and related syndromes ninth. Although both men and women of all age groups can be affected, women outnumber men almost 10 fold and. Sle is characterized by production of pathogenic autoantibodies. Systemic lupus erythematosus sle is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Dubois lupus erythematosus and related syndromes ninth edition. By 3 months of age, most female transgenics develop a lupuslike syndrome characterised by production of igg antidsdna, antihistone and antinucleosome autoantibodies. Systemic lupus erythematosus sle is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. Multiple genes contribute to disease susceptibility.
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. Systemic lupus erythematosus is a systemic autoimmune disease with a worldwide distribution. Isbn 9789535102663, pdf isbn 9789535168928, published 20120321. Although recognized over 140 years ago when kaposi recorded the systemic nature and. Progranulin pgrn is an immunomodulatory protein that is upregulated in sle patients. While previously it was thought to be primarily antibodydriven, it is now known that all parts of the immune system contribute to the pathogenesis of the disease. Systemic lupus erythematosus sle is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations. Environmental factors that may be relevant in the pathogenesis of systemic lupus erythematosus.
The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of sle, and to investigate the mechanism involved. Genomewide association studies gwas have progressively improved understanding of which genes are most. Systemic lupus erythematosus sle is a remarkably complex and heterogeneous systemic autoimmune disease. Taming lupus a new understanding of pathogenesis is leading to clinical advances. Gut microbiota promote the inflammatory response in the. Systemic lupus erythematosus, or lupus, is an autoimmune systemic disease that can affect many organ systems in many different ways. 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. It can be life threatening when major organs are involved. Introduction systemic lupus erythematosus sle is a multi system connective tissue disorder characterized by the presence of.
The present paper describes the current concepts in the mechanisms, genomics, and pathogenesis of sle and their implications. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated. 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. Taken together, these data identify shp2 as a critical regulator of sle pathogenesis and suggest targeting of its activity as a potent treatment for lupus. An update on pathogenesis of systemic lupus erythematosus. Systemic lupus erythematosus sle is a complex clinical syndrome, elements of which remain poorly understood. Systemic lupus erythematosus sle is an autoimmune disease characterized by excessive autoantibody production and multiorgan involvement. Mouse models of systemic lupus erythematosus reveal a. Moulton,1, abel suarezfueyo,1 esra meidan,1,2 hao li. Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskel etal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and. Pathogenesis of systemic lupus erythematosus journal of clinical. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated. Chance, genetics, and the heterogeneity of disease and. One such autoimmune diseasesystemic lupus erythematosusis characterized by the loss of b and tcell tolerance to selfantigens principally nuclear, culminating in multisystemic inflammation.
The exact pathoaetiology of systemic lupus erythematosus sle remains elusive. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is. The aim of this study was to repurpose metformin, an antidiabetic drug that regulates systemic and cellular metabolism, and assess its effects in chinese patients with sle without diabetes. Expires july 31, 2017 systemic lupus erythematosus sle is a chronic autoimmune disease that often goes undiagnosed initially. 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. Timely detection of sle is important, because prompt treatment can prevent its many major complicationsnotably, end organ damage.
This book will provide an introduction to the epidemiology, etiology and pathogenesis of the condition while also exploring the classification, diagnosis, and current and emerging therapies for systemic lupus erythematosus. Systemic lupus erythematosus sle is a chronic, occasionally lifethreatening, multisystem disorder. A diverse array of genetic factors contribute to the. Multiple functions of b cells in the pathogenesis of systemic lupus. Therefore, before we go on to discuss what goes wrong in the immune system of lupus. 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 systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. Moreover, in cultured human lupus t cells, shp2 inhibition reduced proliferation and decreased production of ifn. Due to its complex and only partly understood etiology, 1 systemic lupus erythematosus sle has been labeled the cruel mystery by the lupus foundation of america.
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