The structural features of the interaction between DNA and lupus anti-DNA antibodies were investigated by competition experiments with low molecular weight synthetic compounds. It was found that two correctly spaced chemical components, a substituted aromatic ring system and a negatively charged acidic residue, were required for the binding of most anti-DNA autoantibodies to their respective antigens. These chemical elements are combined in the structure of several anionic dyes, including some certified food colours. The dyes were found to interfere efficiently and specifically with the lupus DNA-anti-DNA immune reaction. Therefore, this family of compounds may serve as a basis for the development of a new approach to drug therapy in SLE.
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Ann Rheum Dis
June 2024
InsideOutBio Inc, Charlestown, Massachusetts, USA.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by antibodies to DNA (anti-DNA) and other nuclear macromolecules. Anti-DNA antibodies are markers for classification and disease activity and promote pathogenesis by forming immune complexes that deposit in the tissue or stimulate cytokine production. Studies on the antibody response to DNA have focused primarily on a conformation of DNA known as B-DNA, the classic right-handed double helix.
View Article and Find Full Text PDFArthritis Rheumatol
September 2024
Duke University Medical Center and Durham Veterans Administration Medical Center, Durham, North Carolina.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies [ANAs]). These antibodies can bind to DNA, RNA, and protein complexes with nucleic acids.
View Article and Find Full Text PDFJ Transl Autoimmun
December 2019
GIRAT: Grupo de Investigación en Reumatología, Autoinmunidad y Medicina Traslacional, Fundación Valle Del Lili and Universidad Icesi, Cali, Colombia.
Clin Exp Immunol
February 2020
Department of Immunopathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
There have been many studies on the mechanisms of internalization of DNA-anti-DNA immune complexes by cells, including the one used for rheumatoid factor-expressing mouse B cells. In parallel, studies on the role of intracellular DNA sensors in the pathogenesis of systemic lupus erythematosus (SLE) have been conducted, including the one using a mouse model lacking one of the sensors. These and other data have established a framework for understanding the pathogenic role of anti-DNA antibodies, but studies on normal cells are limited.
View Article and Find Full Text PDFFront Immunol
October 2020
Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital of Giessen and Marburg, Justus Liebig University Giessen, Giessen, Germany.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by the production of autoantibodies specific for components of the cell nucleus and that causes damage to body tissues and organs. The pathogenesis of SLE remains unclear, with numerous studies pointing to a combination of genetic and environmental factors. A critical stage in SLE development is cell necrosis, in which undegraded chromatin and nucleoproteins are released into the blood, resulting in circulating cell-free DNA and serum nucleoproteins that trigger anti-dsDNA autoantibody production.
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