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DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the Pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a perplexing and potentially severe disease, the pathogenesis of which is yet to be understood. SLE is considered to be a multifactorial disease, in which genetic factors, immune dysregulation, and environmental factors, such as ultraviolet radiation, are involv...

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Detalles Bibliográficos
Autores principales: Mireles-Canales, Martha Paola, González-Chávez, Susana Aideé, Quiñonez-Flores, Celia Maria, León-López, Ever Adán, Pacheco-Tena, César
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079408/
https://www.ncbi.nlm.nih.gov/pubmed/30116756
http://dx.doi.org/10.1155/2018/8214379
Descripción
Sumario:Systemic lupus erythematosus (SLE) is a perplexing and potentially severe disease, the pathogenesis of which is yet to be understood. SLE is considered to be a multifactorial disease, in which genetic factors, immune dysregulation, and environmental factors, such as ultraviolet radiation, are involved. Recently, the description of novel genes conferring susceptibility to develop SLE even in their own (monogenic lupus) has raised the interest in DNA dynamics since many of these genes are linked to DNA repair. Damage to DNA induces an inflammatory response and eventually triggers an immune response, including those targeting self-antigens. We review the evidence that indicates that patients with SLE present higher levels of DNA damage than normal subjects do and that several proteins involved in the preservation of the genomic stability show polymorphisms, some of which increase the risk for SLE development. Also, the experience from animal models reinforces the connection between DNA damage and defective repair in the development of SLE-like disease including characteristic features such as anti-DNA antibodies and nephritis. Defining the role of DNA damage response in SLE pathogenesis might be strategic in the quest for novel therapies.