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A Diverse Array of Genetic Factors Contribute to the Pathogenesis of Systemic Lupus Erythematosus

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Review

A Diverse Array of Genetic Factors Contribute to the Pathogenesis of Systemic Lupus Erythematosus

Nicki Tiffin et al. Orphanet J Rare Dis.

Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number variation have also been identified; and an effect of ethnicity on susceptibility has been described.

Figures

Figure 1
Figure 1
Stages in the pathogenesis of SLE. Environmental triggers (hormones, viruses etc.) and genetic factors along with other chance events, act on the immune system to initiate autoimmunity. Symptoms of clinical illness appear soon after pathogenic autoimmunity develops.
Figure 2
Figure 2
General hypothesis for the pathogenesis of SLE. Increased production of apoptotic blebs and/or reduced clearance of apoptotic blebs lead to the release of chromatin into the circulation. Presence of chromatin in circulation leads to the activation of antigen-presenting cells (APCs) and the formation of pathogenic immune complexes that incite glomerulonephritis. From Munoz et al. 2008 [20], copyright © 2011 by SAGE Publishing, reprinted by permission of SAGE.
Figure 3
Figure 3
Network analysis of known SLE-associated genes. Network analysis using Ingenuity Pathway Analysis software shows regulatory interactions between almost half of the known SLE-associated genes, shown as shaded molecules. Three sub-networks are circled. Potential regulatory partners that participate in the networks but are not previously associated with SLE are shown as non-shaded molecules. Several IgG molecules have multiple interactions with network members, shown as dotted lines.

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