Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recent advances in the genetics of systemic lupus erythematosus.

ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of antinuclear autoantibodies and the inflammatory infiltration of many organ systems. SLE is a complex disorder in which multiple genetic variants, together with environmental and hormonal factors, contribute to disease risk. In this article, we summarize our current understanding of the genetic contribution to SLE in light of recent genome-wide association studies, which have brought the total number of confirmed SLE susceptibility loci to 29. In the second section, we explore the functional implications of these risk loci and, in particular, highlight the role that many of these genes play in the Toll-like receptor and type I interferon signaling pathways. Finally, we discuss the genetic overlap between SLE and other autoimmune and inflammatory conditions as several risk loci are shared among multiple disorders, suggesting common underlying pathogenic mechanisms.

SUBMITTER: Flesher DL

PROVIDER: S-EPMC2897739 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Recent advances in the genetics of systemic lupus erythematosus.

Flesher Donna L Thibault DL Sun Xin X Behrens Timothy W TW Graham Robert R RR Criswell Lindsey A LA

Expert review of clinical immunology 20100501 3

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of antinuclear autoantibodies and the inflammatory infiltration of many organ systems. SLE is a complex disorder in which multiple genetic variants, together with environmental and hormonal factors, contribute to disease risk. In this article, we summarize our current understanding of the genetic contribution to SLE in light of recent genome-wide association studies, which have brought the total n ...[more]

PMID: 20441431

Similar Datasets

Recent advances in the management of systemic lupus erythematosus.

Project description:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being achieved. Emerging evidence has allowed the development of new biological therapeutic options targeting crucial molecular mediators involved in the pathogenesis of SLE. This literature review analyzes the availability of biological and target-directed treatments, phase II and III trials, and new therapies that are being developed for the treatment of SLE.

| S-EPMC6039948 | biostudies-literature

Advances in drug therapy for systemic lupus erythematosus.

Project description:Systemic lupus erythematosus (SLE) is an autoimmune disorder that afflicts 500,000 people in the United States. There has not been a new SLE drug approved in the United States since 1958. However, a guidance document issued by the Food and Drug Administration in 2005 provided a roadmap for investigators which spawned numerous ongoing clinical trials. Among these, Belimumab, a monoclonal antibody to soluble B lymphocyte stimulator, met its primary endpoints in two large trials and will probably obtain FDA approval soon. Other promising agents targeting a variety of mechanisms of action are currently in development. This minireview highlights the latest therapies under investigation in SLE and gives an overview of the pathways that are specifically being targeted.

| S-EPMC3009611 | biostudies-literature

Genetics of systemic lupus erythematosus and Sjogren's syndrome.

Project description:Purpose of reviewTo determine the advances made in the genetics of systemic lupus erythematosus (SLE) or Sjögren's syndrome as the era of genome-wide association and high-throughput single nucleotide typing begins.Recent findingsSeveral genome-wide association studies have been performed in SLE but there are no such studies published or in progress for Sjögren's syndrome. Genetics and the functional significance of risk alleles in the interferon pathway are being worked out in detail. This is especially true for STAT4 and IRF5. Gene copy number variation, a major source of genetic variability, is important for several genes that impart risk for SLE. An X chromosome copy number dose effect has recently been identified. Genetic evaluation of Sjögren's syndrome is limited to small studies that have concentrated on genes already shown to be risk factors in SLE.SummaryKnowledge of the genetics of SLE is advancing rapidly, whereas that of Sjögren's syndrome lags behind considerably.

| S-EPMC8056840 | biostudies-literature

Therapeutic options for cutaneous lupus erythematosus: recent advances and future prospects.

Project description:Treatment and prevention are of critical importance in patients with cutaneous lupus erythematosus (CLE), as the disease can have a devastating effect on patient well-being and quality of life.We conducted a selective search of the PubMed database for articles published between December 2010 and November 2015. This review encompasses both non-pharmaceutical (photoprotection, smoking cessation, drug withdrawal, and vitamin D replacement) and pharmaceutical (topicals, antimalarials, immunosuppressives, biologics, etc.) interventions used in the treatment of CLE. Expert Commentary: Recent work has expanded our understanding of established therapies as well as introduced new treatments for consideration, though existing medications still prove inadequate for a subset of patients. Changes in trial design may help to alleviate this issue.

| S-EPMC5843480 | biostudies-other

Recent insights into the genetic basis of systemic lupus erythematosus.

Project description:Genetic variation was first shown to be important in systemic lupus erythematosus (SLE or lupus) in the 1970s with associations in the human leukocyte antigen region. Almost four decades later, and with the help of increasingly powerful genetic approaches, more than 25 genes are now known to contribute to the mechanisms that predispose individuals to lupus. Over half of these loci have been discovered in the past 2 years, underscoring the extraordinary success of genome-wide association approaches in SLE. Well-established risk factors include alleles in the major histocompatibility complex region (multiple genes), IRF5, ITGAM, STAT4, BLK, BANK1, PDCD1, PTPN22, TNFSF4, TNFAIP3, SPP1, some of the Fcgamma receptors, and deficiencies in several complement components, including C1q, C4 and C2. As reviewed here, many susceptibility genes fall into key pathways that are consistent with previous studies implicating immune complexes, host immune signal transduction and interferon pathways in the pathogenesis of SLE. Other loci have no known function or apparent immunological role and have the potential to reveal novel disease mechanisms. Certainly, as our understanding of the genetic etiology of SLE continues to mature, important new opportunities will emerge for developing more effective diagnostic and clinical management tools for this complex autoimmune disease.

| S-EPMC3144759 | biostudies-literature

Recent insights into the genetic basis of systemic lupus erythematosus.

Project description:Many identified genetic risk factors for systemic lupus erythematosus (SLE) contribute to the function of the immune system, which has expanded our understanding of disease pathogenesis. We outline the genetic variants in recently identified SLE-associated loci, the immunological pathways affected by these gene products and the disease manifestations linked to these loci. Pathways potentially influenced by SLE risk variants include: apoptosis, DNA degradation and clearance of cellular debris; antigen presentation; type I interferon, Toll-like receptor and nuclear factor kappa κB activation; defective clearance of immune complexes containing nuclear antigens; B and T-cell function and signalling; and monocyte and neutrophil function and signalling. These identified SLE susceptibility loci are predominantly common variants that have been confirmed among multiple ancestries, suggesting shared mechanisms in disease aetiology. Ongoing genetic studies continue the investigation of specific functional variants, and their potential consequences on immune dysregulation, enhancing our understanding of links between genotypes and specific disease manifestations. The next generation of sequencing explores the identification of causal rare variants that may contribute robust genetic effects to developing SLE. Novel insights coming from genetic studies of SLE provide the opportunity to elucidate pathogenic mechanisms as well as contribute to the development of innovative therapeutic targets for this complex disease.

| S-EPMC3780983 | biostudies-literature

Systemic lupus erythematosus

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-03 | E-GEOD-46923 | biostudies-arrayexpress

Genetics of the type I interferon pathway in systemic lupus erythematosus.

Project description:Genetic studies of systemic lupus erythematosus (SLE) have been successful, identifying numerous risk factors for human disease. While the list is not yet complete, it is clear that important immune system pathways are represented, one of which being type I interferon (IFN). Circulating type I IFN levels are high in SLE patients and this IFN pathway activation is heritable in families with SLE. We summarize our current understanding of the genetics of the type I IFN pathway in SLE, with an emphasis on studies that demonstrate an impact of the SLE-risk alleles upon type I IFN pathway activation in SLE patients. These studies illustrate that variations in type I IFN pathway genes represent a common genetic feature of SLE. By understanding the genetic regulation of type I IFN, we may be able to intervene in a more personalized fashion, based upon the molecular dysregulation present in a given individual.

| S-EPMC3885171 | biostudies-literature

Recent developments in systemic lupus erythematosus pathogenesis and applications for therapy.

Project description:PURPOSE OF REVIEW:Systemic lupus erythematosus (SLE) pathogenesis is complex. Aberrancies of immune function that previously were described but not well understood are now becoming better characterized, in part through recognition of monogenic cases of lupus-like disease. RECENT FINDINGS:We highlight here recent descriptions of metabolic dysfunction, cytokine dysregulation, signaling defects, and DNA damage pathways in SLE. Specifically, we review the effects of signaling abnormalities in mammalian target of rapamycin, Rho kinase, Bruton's tyrosine kinase, and Ras pathways. The importance of DNA damage sensing and repair pathways, and their influence on the overproduction of type I interferon in SLE are also reviewed. SUMMARY:Recent findings in SLE pathogenesis expand on previous understandings of broad immune dysfunction. These findings have clinical applications, as the dysregulated pathways described here can be targeted by existing and preclinical therapies.

| S-EPMC6050980 | biostudies-literature

Systemic lupus erythematosus

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-06-03 | GSE46923 | GEO