Treatment of mild, moderate, and severe lupus erythematosus: focus on new therapies.

University of California, San Francisco, USA.
Current Rheumatology Reports (Impact Factor: 2.45). 05/2011; 13(4):308-16. DOI: 10.1007/s11926-011-0186-6
Source: PubMed

ABSTRACT Despite large-scale efforts devoted to the conduct of clinical trials in systemic lupus erythematosus (SLE), no new therapy has been approved for treatment of this disease in more than 50 years. Increased understanding of the immunologic mechanisms underlying SLE has led to the development of a variety of biologic agents that target specific aspects of the adaptive and innate arms of the immune system, including B cells, T cells, dendritic cells, and various cytokines. One of these agents, belimumab, was the subject of two positive phase 3 trials in nonrenal lupus that have given us hope that a new therapy for SLE may be finally within our grasp. In addition to these newer therapies, recent studies of standard-of-care medications such as mycophenolate mofetil and hydroxychloroquine have better defined the efficacy and safety of these agents for the treatment of lupus nephritis and nonrenal lupus. This article provides a discussion of several novel biologic agents at different stages of development for the treatment of SLE, as well as an analysis of newer data on agents that have been used in the treatment of SLE for many years.

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    • "The clinical presentation of SLE is influenced by a variety of factors including ethnicity, gender, age, socioeconomic factors, and age of onset [1]. The typical course of the disease is illustrated by periods of disease flares alternating with waning disease activity, and the typical treatment of SLE consists of immunosuppressive medication, which clinically improves the condition of the patients [7]. The etiology of SLE is believed to be multifactorial with genetic and environmental factors, both contributing to the development of this very complex disease. "
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    ABSTRACT: The etiology of SLE is not fully established. SLE is a disease with periods of waning disease activity and intermittent flares. This fits well in theory to a latent virus infection, which occasionally switches to lytic cycle, and EBV infection has for long been suspected to be involved. This paper reviews EBV immunobiology and how this is related to SLE pathogenesis by illustrating uncontrolled reactivation of EBV as a disease mechanism for SLE. Studies on EBV in SLE patients show enlarged viral load, abnormal expression of viral lytic genes, impaired EBV-specific T-cell response, and increased levels of EBV-directed antibodies. These results suggest a role for reactivation of EBV infection in SLE. The increased level of EBV antibodies especially comprises an elevated titre of IgA antibodies, and the total number of EBV-reacting antibody isotypes is also enlarged. As EBV is known to be controlled by cell-mediated immunity, the reduced EBV-specific T-cell response in SLE patients may result in defective control of EBV causing frequent reactivation and expression of lytic cycle antigens. This gives rise to enhanced apoptosis and amplified cellular waste load resulting in activation of an immune response and development of EBV-directed antibodies and autoantibodies to cellular antigens.
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    ABSTRACT: Systemic lupus erythematosus is a complex human disease likely influenced by a compilation of necessary, but not individually sufficient, features. Although many genetic and environmental factors are associated, this review will focus on the evolving evidence for key Epstein-Barr virus specific roles. Recent studies have shown additional molecular mimicry mechanisms between early events in lupus autoimmunity and specific Epstein-Barr virus responses. In addition, several recent papers have demonstrated increased Epstein-Barr viral load, increased numbers of latently infected peripheral B cells, impaired functional T cell responses, and association of the presence of Epstein-Barr virus DNA in systemic lupus erythematosus patients compared with controls. Additional work has continued to show association of various aspects of Epstein-Barr virus serology with systemic lupus erythematosus and a recent paper outlines differences in the pediatric systemic lupus erythematosus humoral immune response to Epstein-Barr virus nuclear antigen-1 compared with matched controls. This review will briefly outline the recent advances that show serologic, DNA, gene expression, viral load, T cell responses, humoral fine specificity, and molecular mimicry evidence for differences between systemic lupus erythematosus patients and controls and the impact that these findings have on understanding the role of Epstein-Barr virus in systemic lupus.
    Current Opinion in Rheumatology 10/2006; 18(5):462-7. DOI:10.1097/01.bor.0000240355.37927.94 · 5.07 Impact Factor
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    ABSTRACT: Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs) on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3), hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.
    PLoS ONE 07/2012; 7(7):e40862. DOI:10.1371/journal.pone.0040862 · 3.53 Impact Factor