Targeting of the immune system in systemic lupus erythematosus

2008 ◽  
Vol 10 ◽  
Author(s):  
Meera Ramanujam ◽  
Anne Davidson
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Immune Modulation ◽  
New Drugs ◽  
Systemic Lupus ◽  
Immune Disorder ◽  
Treatment Regimens ◽  
New Treatment ◽  
Activation Pathways

Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other crossreactive antigens is associated with the development of pathogenic autoantibodies that damage target organs, including the skin, joints, brain and kidney. New drugs based on modulation of the immune system are currently being developed for the treatment of SLE. Many of these new therapies do not globally suppress the immune system but target specific activation pathways relevant to SLE pathogenesis. Immune modulation in SLE is complicated by differences in the immune defects between patients and at different disease stages. Since both deficiency and hyperactivity of the immune system can give rise to SLE, the ultimate goal for SLE therapy is to restore homeostasis without affecting protective immune responses to pathogens. Here we review recent immunological advances that have enhanced our understanding of SLE pathogenesis and discuss how they may lead to the development of new treatment regimens.

scholarly journals The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

2021 ◽  
Vol 10 (2) ◽  
pp. 243
Author(s):  
Matteo Piga ◽  
Laurent Arnaud
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Systemic Lupus ◽  
Major Step ◽  
Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

Efficacy of Danazol with Autoimmune Thrombocytopenia

1997 ◽  
Vol 3 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Steven W. Kim ◽  
Lawrence Rice ◽  
John J. McCarthy
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Evans Syndrome ◽  
Systemic Lupus ◽  
Autoimmune Thrombocytopenia ◽  
Treatment Regimens ◽  
Duration Of Disease ◽  
Males And Females ◽  
The Mean ◽  
Favorable Side Effect Profile

Seventy-nine cases of autoimmune thrombocytopenia seen by the Baylor Hematology section of The Methodist Hospital between 1991 and 1996 were retrospectively reviewed to assess the effectiveness of danazol in the treatment of autoimmune thrombocytopenia. Among the 42 patients who received danazol, the mean initial platelet count prior to treatment was 24.3 ± 17.4 (SD) × 109/L with a mean duration of disease of 53 months. Most cases were idiopathic, but some patients had underlying secondary disorders (rheumatoid arthritis, systemic lupus erythematosus, HIV, and/or Evans' syndrome). Overall 57% of the patients treated with danazol had an excellent or a good response with three patients who had unmaintained remission for >11 months. Minimal side effects were noted. Fifty percent of the patients with associated secondary disorders achieved an excellent or good response. The hemolytic component of all three Evans' syndrome cases was well controlled with danazol. In two cases, danazol was effective where a variety of other treatment regimens were not. An excellent or a good response was found in 58%, 62%, and 53% in patients >65 years old, between 45 and 65 years old, and <45 years old, respectively. Response rates were similar in males and females, Seventy percent of the nonsplenectomized patients had an excellent or a good response compared to 33% in postsplenectomy patients. Overall in view of its favorable side-effect profile, it is rational early on to attempt to abrogate the need for splenectomy, it may salvage splenectomy failures, and there is a reasonable response rate in those refractory to multiple prior therapies. Key Words: Autoimmune thrombocytopenia—Idiopathic thrombocytopenic purpura—Danazol— Systemic lupus erythematosus—HIV—Evans' syndrome.

scholarly journals Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis

2021 ◽  
Vol 22 (8) ◽  
pp. 4194
Author(s):  
Martina Mazzariol ◽  
Giovanni Camussi ◽  
Maria Felice Brizzi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Extracellular Vesicles ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Coagulation Cascade ◽  
Renal Diseases ◽  
Systemic Lupus

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.

scholarly journals Systemic Lupus Erythematosus Disease: An Overview of the Clinical Approach to Pathogenesis, Diagnosis, and Treatment

2021 ◽  
Vol 4 (2) ◽  
pp. 91-98
Author(s):  
Saurabh Nimesh ◽  
Md. Iftekhar Ahmad ◽  
Shikhka Dhama ◽  
Pradeep Kumar ◽  
Muhammad Akram ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Chronic Disease ◽  
Lupus Erythematosus ◽  
The Body ◽  
Clinical Approach ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus ◽  
Organ Systems ◽  
Novel Approaches

The systemic lupus erythematosus (SLE), commonly known as Lupus, is a rare and complex multisystem autoimmune disease where one’s immune system is overactive, and the body attacks its organ systems. SLE is a historically old disease described already in antiquity; it is an example of a chronic disease with physical, psychological, financial, and social implications for individuals diagnosed. It has inspired medical and basic biological scientists that focus on molecular biology, basic immunology, immunopathology, clinical science, genetics, and epidemiology. The syndrome is real in its existence-although hidden behind obstacles, cumbersome for patients and clinicians, and rebellious for scientists. There is currently no cure for SLE. The goal of treatment is to ease symptoms. This article will review information on the general approach to SLE therapy, focusing on currently approved therapies and novel approaches that might be used in the future.

Juvenile-onset systemic lupus erythematosus

2013 ◽  
pp. 948-956
Author(s):  
Louise Watson ◽  
Michael W. Beresford
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Family Involvement ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Juvenile Onset ◽  
Host Immune Responses ◽  
American College Of Rheumatology ◽  
Organ Manifestations ◽  
New Treatment ◽  
Onset Systemic Lupus Erythematosus

Paediatric or juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune condition, differing from the adult form in terms of severity, organ manifestations, and a less striking female predominance. The diagnosis relies on the adult-derived American College of Rheumatology SLE classification criteria. Genetic, autoantibody, and host immune responses, characteristic of this disease, result in a clinically heterogeneous phenotype. A proportion of paediatric SLE patients will have evidence of a genetic deficiency known to be associated with SLE, such as C1q deficiency, and screening for these is required. A challenging diagnosis to make in the younger age group, the management of JSLE compared to adult-onset SLE requires special consideration towards the significant long-term consequences of the disease and treatment toxicity, combined with an onset during a fundamental time with regards to growth and development. A comprehensive, multidisciplinary team approach to the management of JSLE is essential. With a more severe phenotype and limited comorbidities, patients with JSLE represent an invaluable opportunity for investigating the pathogenesis. To date, clinical trials informing interventions in JSLE are very limited and treatment choices rely on the outcome of adult trials. Patient and family involvement in research to improve outcomes and understanding is essential. New treatments, including biological therapies, are becoming available for clinical use and new treatment combinations have been used to induce and maintain clinical remission.

scholarly journals Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1641
Author(s):  
Chang-Youh Tsai ◽  
Chieh-Yu Shen ◽  
Chih-Wei Liu ◽  
Song-Chou Hsieh ◽  
Hsien-Tzung Liao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Tissue Damage ◽  
Immune Modulation ◽  
Clinical Manifestations ◽  
Systemic Autoimmune Disease ◽  
Circular Rnas ◽  
Contributing Factors ◽  
Systemic Lupus ◽  
Non Coding Rnas

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with heterogeneous clinical manifestations. A diverse innate and adaptive immune dysregulation is involved in the immunopathogenesis of SLE. The dysregulation of immune-related cells may derive from the intricate interactions among genetic, epigenetic, environmental, and immunological factors. Of these contributing factors, non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs), and long non-coding RNAs (lncRNAs) play critical roles in the post-transcriptional mRNA expression of cytokines, chemokines, and growth factors, which are essential for immune modulation. In the present review, we emphasize the roles of ncRNA expression in the immune-related cells and cell-free plasma, urine, and tissues contributing to the immunopathogenesis and tissue damage in SLE. In addition, the circular RNAs (circRNA) and their post-translational regulation of protein synthesis in SLE are also briefly described. We wish these critical reviews would be useful in the search for biomarkers/biosignatures and novel therapeutic strategies for SLE patients in the future.

Type I Interferons in Autoimmune Disease

2019 ◽  
Vol 14 (1) ◽  
pp. 369-393 ◽  
Author(s):  
Mary K. Crow ◽  
Mikhail Olferiev ◽  
Kyriakos A. Kirou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Systemic Lupus ◽  
Pathway Activation ◽  
Interferon Pathway ◽  
Chronic Activation

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.

The innate immune system in human systemic lupus erythematosus

2017 ◽  
Vol 131 (8) ◽  
pp. 625-634 ◽  
Author(s):  
Marc Weidenbusch ◽  
Onkar P. Kulkarni ◽  
Hans-Joachim Anders
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Innate Immune System ◽  
Innate Immune ◽  
Type I ◽  
Human Systemic Lupus Erythematosus ◽  
Systemic Lupus ◽  
Adaptive Immune

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

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