Treatment of mild, moderate, and severe lupus erythematosus: focus on new therapies.
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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ABSTRACT: Our recent data showed that signal transducers and activators of transcription 1 (STAT1), adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine 10 (CXCL10) were significantly elevated in a systemic lupus erythematosus (SLE) cohort compared to healthy donors. High and low STAT1 subsets were identified in SLE patient visits. The present study analyzed the correlation of common treatments used in SLE with the levels of these biomarkers. Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, of whom 60 had samples from 2 or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real time polymerase chain reaction (PCR) assays. Relative expression of interferon signature genes, CCL2, and CXCL10 were determined by the DeltaDeltaCT method. Results were correlated with therapy using prednisone, mycophenolate mofetil, and hydroxychloroquine and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher's exact test. CCL2 and CXCL10 were significantly higher in untreated patients compared to treated patients, however, in high STAT1 patient visits there is no significant difference between treated and untreated patients' visits. When comparing linear regression fits of interferon (IFN) score with CCL2 and CXCL10, untreated patients and high STAT1 patients displayed significantly higher slopes compared to treated patients. There was no significant difference between the slopes of high STAT1 and untreated patients indicating that CCL2 and CXCL10 were correlated with type-I IFN in high STAT1 patients similar to that in untreated patients. CCL2 and CXCL10 levels in high STAT1 subset remained high in treated patient visits compared to those of the low STAT1 subset. Among the biomarkers analyzed, only CCL2 and CXCL10 showed significantly reduced levels in treated compared to untreated SLE patients. STAT1, CCL2, and CXCL10 are potentially useful indicators of therapeutic action in SLE patients. Further work is needed to determine whether high STAT1 levels convey resistance to therapies commonly used to treat SLE and whether STAT1 inhibitors may have therapeutic implication for these patients.Arthritis research & therapy 01/2014; 16(1):R23. · 4.12 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients.Lupus science & medicine. 04/2014; 1(1):e000015.
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ABSTRACT: Anemia is one of the most common hematological manifestations in SLE patients, occurring in about 50 % of active cases. STAT1 is a critical signaling molecule required for the production of type-1 interferon (I-IFN), CCL2, and CXCL10, all of which are upregulated in SLE. Overexpression of STAT1 has been described to be involved in anemia in animal models. The aim of this study is to analyze how these components are involved in SLE-associated anemia. Blood samples were collected from 39 healthy donors and 101 SLE patients fulfilling ACR criteria. Samples were collected from a total of 180 visits (58 patients had 2 or more visits) of which 52 visits included a diagnosis of anemia. Healthy donors had only single visit. Total RNA, isolated from leukocytes, was analyzed by Taqman qPCR. Relative expression levels of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by the Wilcoxon/Kruskal-Wallis test and Fisher's exact test. Significant increases in IFN score (p < 0.0001), STAT1 (p < 0.0001), miR-146a (p < 0.0005), CCL2 (p = 0.0047), and CXCL10 (p = 0.017), as well as a significant decrease in pri-miR-146a (p = 0.0002), were detected in the anemic SLE patient visits (n = 52) compared to non-anemic SLE visits (n = 128). Regardless of disease activity, lupus nephritis, or race, anemic SLE patients displayed significantly elevated levels of STAT1 and miR-146a compared to non-anemic SLE patients. STAT1 and miR-146a may be upregulated during inflammation and via proinflammatory cytokines and chemokines in SLE. Prolonged upregulation of STAT1 and miR-146a appears to play an important role in anemia in SLE patients.Journal of Clinical Immunology 12/2013; 34(2). · 2.65 Impact Factor