Aetiopathogenesis of systemic lupus erythematosus

2016 ◽  
Author(s):  
Peter Lloyd ◽  
Sarah Doaty ◽  
Bevra H. Hahn
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Adaptive Immune System ◽  
Immune Dysregulation ◽  
Systemic Lupus ◽  
Adaptive Immune ◽  
Loss Of Tolerance ◽  
Three Stages

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of immune dysregulation, autoreactive B and T cells, and the production of a broad, heterogeneous group of autoantibodies (autoAb). The pathogenesis of lupus can be divided into three stages: 1) genetic predisposition and environmental exposures, 2) loss of tolerance, and 3) immune activation. In this chapter we will discuss the aetiopathogenesis of systemic lupus erythematosus with emphasis placed on key autoantibodies, cytokines, the innate and adaptive immune system, tolerance, NETosis, genetics and epigenetics, environmental triggers and the role of gender.

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.

The curious case of miR-155 in SLE

2021 ◽  
Vol 23 ◽  
Author(s):  
S. A. Ibrahim ◽  
A. Y. Afify ◽  
I. O. Fawzy ◽  
N. El-Ekiaby ◽  
A. I. Abdelaziz
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Targeted Therapy ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Recent Attention ◽  
Made In

Abstract Epigenetic modifications have been well documented in autoimmune diseases. MicroRNAs (miRNAs), in particular, have long intrigued scientists in the field of autoimmunity. Owing to its central role in the development of the immune system, microRNA-155 (miR-155) is deeply involved in systemic lupus erythematosus (SLE). Despite the advancements made in treating SLE, the disease still remains incurable. Therefore, recent attention has been drawn to the manipulation of epigenetics in the development of curative treatments. In fact, it is a widely held view that miRNA-targeted therapy is a new glimmer of hope in the treatment of autoimmune diseases. However, the duplicity of miRNAs should not be overlooked. A single miRNA can target several mRNAs, and some mRNAs may possess opposing functions. In this review, we highlight the role of miR-155 as a biomarker and review its functions in SLE patients and animal models while discussing possible reasons behind inconsistencies across studies.

Systemic lupus erythematosus

2018 ◽  
Author(s):  
Chee-Seng Yee
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Adaptive Immune System ◽  
Unknown Etiology ◽  
Inflammatory Disorder ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Cellular Apoptosis

Systemic lupus erythematosus is a chronic multisystem autoimmune inflammatory disorder of unknown etiology. Numerous abnormalities within the innate and adaptive immune system have been described. The hallmark of this disease is B-cell hyperactivity resulting in autoantibody production, abnormal T-cell function, impaired clearance of immune complexes (resulting in their deposition in tissues), complement activation, and defective cellular apoptosis. However, these abnormalities of the immune system are not uniform across patients or within the same patient at different stages of the disease, resulting in heterogeneity in its presentation and progress.

Infection—genetics relationship in systemic lupus erythematosus

Lupus ◽  
2009 ◽  
Vol 18 (13) ◽  
pp. 1169-1175 ◽  
Author(s):  
G. Domenico Sebastiani ◽  
M. Galeazzi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Molecular Mimicry ◽  
Host Cells ◽  
Infectious Agents ◽  
Systemic Lupus ◽  
Altered Expression ◽  
Genetically Determined

Genetic, environmental, and hormonal factors contribute to disease susceptibility in systemic lupus erythematosus. Among environmental factors, infectious agents play a major role. When considering the complex relationship between genetic predisposition and infections in the pathogenesis of systemic lupus erythematosus, we have to consider that infectious agents can interact with the immune system in several ways. For example, molecular mimicry, altered apoptosis of the host cells, exposure of as yet masked antigens to the immune system by a given microorganism, and direct viral invasion of immunocompetent cells are all mechanisms that may give rise to dysfunction of the immune system; in addition, some genetically determined deficit of the immune system, such as complement deficiency or deficit of mannose binding lectine, may cause insufficient clearance of infectious agents, whose persistence in the host may determine autoimmunity. Finally, evidence has been emerging suggesting that the production of autoantibodies, by infected B-lymphocytes, may be drawn by altered expression of particular microRNA in these cells. In this paper, we review some of the distinct scenarios that can account for the role of infectious agents, acting on a genetically prone host, in determining systemic lupus erythematosus.

Immunogenetic studies on systemic lupus erythematosus

Lupus ◽  
2009 ◽  
Vol 18 (10) ◽  
pp. 878-883 ◽  
Author(s):  
GD Sebastiani ◽  
M Galeazzi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Adaptive Immune System ◽  
Working Party ◽  
Systemic Lupus ◽  
Genetic Studies ◽  
Adaptive Immune ◽  
Genome Wide ◽  
European Working ◽  
Multiple Abnormalities

Understanding the pathogenesis of systemic lupus erythematosus (SLE) remains a considerable challenge. Multiple abnormalities of both the innate and adaptive immune system have been described and, furthermore, immunological dysfunction precedes clinical presentation by many years. There is a strong genetic basis to SLE, which means that genetic studies can play a key role in furthering our understanding of this disease. Because susceptibility variants are present from birth and are unaffected by the course of the disease, or by its treatment, genetic analysis is, perhaps uniquely, capable of identifying fundamental, causative, disease mechanisms. In this article, we review our SLE immunogenetic studies performed in collaboration with the European Working Party on Systemic Lupus Erythematosus. By considering the results of our research and the recent advances obtained by genome-wide associations’ studies, we can begin to understand how dysregulation at a number of key immunological steps may predispose to the development of SLE.

The role of microRNAs (MiR-125a and MiR-146a), RANTES, and IFN-γin systemic lupus erythematosus

2020 ◽  
Vol 23 (13) ◽  
Author(s):  
Ikram khazal Qasim Al- hasso ◽  
Aida Rashid Al- Derzi ◽  
Ahmed Abdul-hassan Abbas ◽  
Faiq I. Gorial ◽  
Ahmed Sameer Alnuimi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus

scholarly journals Acute interstitial nephritis and drug-induced systemic lupus erythematosus due to chlorthalidone and amiodarone: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091002 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M Hanna ◽  
Anthony Sisk ◽  
Lama Abdelnour ◽  
Lena Ghobry ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Systemic Lupus ◽  
Drug Induced ◽  
Systemic Manifestations

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

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