Systemic lupus erythematosus (SLE) is a potentially debilitating, chronic autoimmune inflammatory disease that is commonly diagnosed in women of childbearing age. Virtually any organ system can be affected; however, clinical symptoms are usually musculoskeletal, renal, dermatologic, and hematologic. SLE is a clinically variable disease, which can be mild or life-threatening depending on the organs involved.
For the past four decades the available treatments for patients with SLE have remained relatively unchanged, with therapy relying on traditional agents. Although disease manifestations can be effectively controlled in many patients, some fail to respond to treatment and many suffer from severe drug-related side effects.
Research over the past few years, however, means we have entered a new era in the management of SLE. New insights into SLE pathogenesis have led to the development of biological therapies that specifically target key molecules and cells. Greater understanding of the susceptibility to and expression of SLE has also identified the need for new approaches to managing specific patient subgroups. This unique collection of articles aims to translate the latest research developments in the field of SLE into clinical practice.
All of the articles in this Focus are available to subscribers. An NPG library of relevant Reviews, Perspectives, News & Views, Features, Research Papers, Research Highlights, News pieces and commentaries is also provided.
EDITORIAL
The red wolf remains a wily foe
Peter E. Lipsky & Thomas Dörner
doi:10.1038/nrrheum.2010.83
Nature Reviews Rheumatology 6, 307-308 (2010)
REVIEWS
T cells as therapeutic targets in SLE
José C. Crispín, Vasileios C. Kyttaris, Cox Terhorst & George C. Tsokos
doi:10.1038/nrrheum.2010.60
Nature Reviews Rheumatology 6, 317-325 (2010)
Recent advances have shed light on the biochemical and molecular aberrations that lead to the characteristic cytokine production pattern and altered behavior of T cells in systemic lupus erythematosus (SLE). This article reviews how this knowledge helps understand the nature of the SLE T cell, identifies therapeutic targets that deserve further development, and identifies biomarkers of disease activity.
B cells as therapeutic targets in SLE
Iñaki Sanz & F. Eun-Hyung Lee
doi:10.1038/nrrheum.2010.68
Nature Reviews Rheumatology 6, 326-337 (2010)
B cells promote the pathogenesis of systemic lupus erythematosus in a number of ways. In this article, the authors provide an overview of the role of B cells in SLE, review the rationale for targeting these cells and highlight the limitations and challenges of this approach. Current and future agents for globally or selectively targeting B cells in SLE are also outlined.
Cytokines as therapeutic targets in SLE
Lars Rönnblom & Keith B. Elkon
doi:10.1038/nrrheum.2010.64
Nature Reviews Rheumatology 6, 339-347 (2010)
A number of cytokine pathways are important in the disease process of SLE, and several biological agents for SLE have been developed that target different cytokines or their receptors. This Review discusses the rationale for the use of anti-cytokine therapies in SLE, reviews the different agents tested to date, and presents future directions for therapy.
Genetics of SLE: evidence from mouse models
Laurence Morel
doi:10.1038/nrrheum.2010.63
Nature Reviews Rheumatology 6, 348-357 (2010)
Research in mouse models has revealed the complex role of specific loci and genetic interactions in influencing lupus susceptibility and expression, implicating various pathways in the immunopathogenesis of SLE. This article provides an overview of this complex area and highlights how unraveling the genetic basis of the disease will depend on studies in both mice and humans.
Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations
George K. Bertsias & Dimitrios T. Boumpas
doi:10.1038/nrrheum.2010.62
Nature Reviews Rheumatology 6, 358-367 (2010)
Neuropsychiatric manifestations are common in patients with SLE, encompass a wide range of neurologic and psychiatric features, and can lead to considerable morbidity and mortality. This Review discusses the challenges associated with the diagnosis and treatment of neuropsychiatric SLE.
PERSPECTIVES
Microparticles as autoadjuvants in the pathogenesis of SLE
David S. Pisetsky & Peter E. Lipsky
doi:10.1038/nrrheum.2010.66
Nature Reviews Rheumatology 6, 368-372 (2010)
In the extracellular space, DNA and RNA can function as immunostimulatory molecules, inducing the production of type I interferon, an important mediator in the pathogenesis of SLE. Nucleic acid autoantigens can also be displayed in or on small, membrane-bound vesicles, which might enable these autoantigen-containing microparticles to function as autoadjuvants that can affect the immune system and influence B-cell fate.
Using genetics to deliver personalized SLE therapy—a realistic prospect?
Benjamin Rhodes & Timothy J. Vyse
doi:10.1038/nrrheum.2010.67
Nature Reviews Rheumatology 6, 373-377 (2010)
Major developments in our knowledge of the genetic basis of SLE in the past few years have opened many potential avenues of research. In this article, the authors question whether these advances have been sufficient to fulfill early predictions that genetics can be used to provide personalized healthcare.
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