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New insights into the immunopathogenesis of systemic lupus erythematosus
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New insights into the immunopathogenesis of systemic lupus erythematosus
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Journal Article
New insights into the immunopathogenesis of systemic lupus erythematosus
2016
Overview
Key Points
Our understanding of the pathogenesis of systemic lupus erythematosus (SLE) has changed rapidly over the past decade
Refinements in our understanding over the past 3 years have led to the potential for precision targeting of therapeutic strategies
Advances in epigenetic therapeutic agents and the manipulation of cells
ex vivo
have the potential to further improve patient care
In this Review, Tsokos
et al
. describe recent advances in our understanding of systemic lupus erythematosus (SLE) that are driving repurposing of existing drugs as well as development of new treatments. Cytokines, tolerance pathways, local tissue mediators, and epigenetic mechanisms all show promise as novel targeted therapies that could lead to individualized care in SLE.
The aetiology of systemic lupus erythematosus (SLE) is multifactorial, and includes contributions from the environment, stochastic factors, and genetic susceptibility. Great gains have been made in understanding SLE through the use of genetic variant identification, mouse models, gene expression studies, and epigenetic analyses. Collectively, these studies support the concept that defective clearance of immune complexes and biological waste (such as apoptotic cells), neutrophil extracellular traps, nucleic acid sensing, lymphocyte signalling, and interferon production pathways are all central to loss of tolerance and tissue damage. Increased understanding of the pathogenesis of SLE is driving a renewed interest in targeted therapy, and researchers are now on the verge of developing targeted immunotherapy directed at treating either specific organ system involvement or specific subsets of patients with SLE. Accordingly, this Review places these insights within the context of our current understanding of the pathogenesis of SLE and highlights pathways that are ripe for therapeutic targeting.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 692/420
/ Acids
/ Animals
/ Antigen-Antibody Complex - immunology
/ Antigens
/ Bacteria
/ Biofilms
/ Dendritic Cells - immunology
/ Disease
/ Extracellular Traps - immunology
/ Genetic Predisposition to Disease
/ Humans
/ Immune Tolerance - immunology
/ Lupus
/ Lupus Erythematosus, Cutaneous - immunology
/ Lupus Erythematosus, Systemic - genetics
/ Lupus Erythematosus, Systemic - immunology
/ Lupus Erythematosus, Systemic - therapy
/ Lupus Nephritis - immunology
/ Lupus Vasculitis, Central Nervous System - immunology
/ Mice
/ Systemic lupus erythematosus
