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Medical Specialties / Rheumatology / Systemic Lupus Erythematosus


mTOR Signaling: A Central Pathway to Pathogenesis in Systemic Lupus Erythematosus?

Abstract: Systemic lupus erythematosus (SLE) is a common autoimmune disease with unclear etiology. Treatments for it often provide inadequate control of disease activity or are limited by side effects. Recent studies have shown that rapamycin can be an effective treatment in both murine lupus models and human SLE. We demonstrated that rapamycin could directly alter molecular abnormalities in SLE T cells related to calcium signaling but not mitochondrial function. However, in light of increased knowledge of the role of mammalian target of rapamycin (mTOR) signaling throughout the immune system, several other potential sites of rapamycin action have been revealed. Specifically, mTOR regulates the production of interferon-α and the maintenance of immune tolerance at the level of the regulatory T cell and the dendritic cell, and can promote Th1 versus Th2 immune responses. Thus mTOR offers a window into diverse facets of SLE pathogenesis as well as a potentially unifying narrative in our understanding of diverse facets of the disease. ... Read more

Vaccines and Autoimmune Diseases of the Adult

Abstract: Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following human papilloma virus vaccine. ... Read more

Biologic Therapy for Systemic Lupus Erythematosus

Abstract: A new era in the treatment of systemic lupus erythematosus (SLE) may be dawning. Twelve years after the first approval of biologic therapy for patients with rheumatoid arthritis, the positive results of two large trials of a novel biologic therapy for SLE have raised hopes that a new approach to treatment may be at hand. This encouraging news follows several disappointments in trials of other biologic therapies and provides a timely moment to reflect on where we stand, what we have learned, and what may lie ahead. ... Read more

Natural Autoantibodies to Apoptotic Cell Membranes Regulate Fundamental Innate Immune Functions and Suppress Inflammation

Abstract: The evolution of the immune system has provided a multilevel system that interconnects the innate and adaptive immune systems to serve at least three central purposes: the defense from microbial pathogens, the capacity for discrimination of self- from non-self necessary for the prevention of autoimmune disease, and essential effector roles in wound repair and tissue remodeling. In recent studies, we have elucidated an unsuspected role for a class of naturally occurring autoreactive antibodies from the most primitive tier of B lymphocytes, which regulates fundamental functions of the innate immune system. Our findings also throw light onto long unresolved mysteries regarding the origins of the earliest waves of B lymphocyte development. ... Read more

The Busy Life of Regulatory T Cells in Systemic Lupus Erythematosus

Abstract: CD4+CD25+Foxp3+ regulatory T (Treg) cells suppress the proliferation and release of cytokines in several subsets of immune cells. By doing so and by maintaining immune tolerance in peripheral tissues, Treg cells contribute to avert autoimmunity. Many studies have investigated how Treg cells operate in autoimmune diseases, and which cellular and molecular pathways are targeted by Treg cells. This review provides an update on the activities of Treg cells in systemic lupus erythematosus (SLE), an autoimmune disease characterized by the presence of hyperactive immune cells and aberrant antibody responses to multiple nuclear and cytoplasmic antigens. ... Read more

Genetic Progress Towards the Molecular Basis of Common Autoimmunity

Abstract: Identification of the genetic determinants that underlie autoimmune diseases implicates new biochemical pathways in disease pathogenesis. The authors describe how recent advances in genetic knowledge of autoimmunity have pointed to aberrant negative regulation of autoreactive T-cells as a key step in autoimmunity. The tissue specificity of autoimmune attack is also under genetic control and variations in tissue-specific factors also appear to have a role. ... Read more

Malignancy Risk in Autoimmune Rheumatic Diseases

Abstract: Autoimmune diseases are chronic disorders and are highly prevalent in the population. It is thus logical to see whether patients with autoimmune rheumatic diseases are more prone to cancer. Studies show that most autoimmune diseases are not linked to cancer. However, patients with rheumatic arthritis or systemic lupus erythematosus do have an increased risk for lymphoma. ... Read more

Crypticity of Self Antigenic Determinants Is the Cornerstone of a Theory of Autoimmunity

Abstract: Self antigens can have dominant and cryptic (hidden) antigenic determinants. T cells that can see the dominant antigenic determinants are tolerized and "disarmed." T cells that may still see the cryptic determinants are active and become a part of the T cell repertoire. Under certain circumstances when these T cells are more capable of "seeing" the cryptic antigenic determinants or the cryptic determinants unveil themselves, autoimmunity ensues. ... Read more

Seasonal Variation of Rheumatic Diseases

Abstract: Rheumatic diseases vary by season in severity. Of course, environmental factors, such as temperature and moisture, contribute to the seasonality of some diseases. But other important factors, including as levels of hormones, antibodies, inflammatory factors, and immune response readiness, could greatly contribute to disease seasonalities. ... Read more

Systemic Lupus Erythematosus (SLE): Trials and Issues

Abstract: Lupus is believed to be an autoimmune disease, affecting many more women than men. Patients develop immune responses to self DNA, omnipresent in the body. Estrogen and androgen are involved in the disease. Immunosuppression and sex hormone therapeutics are two major classes of drugs in clinical trials. ... Read more

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