An anti-DNA antibody prefers damaged dsDNA over native

Akberova, N. I.; Zhmurov, Artem; Невзорова, Т. А.; Litvinov, Rustem I.

doi:10.1080/07391102.2015.1128979

Cited by 7 publications

(3 citation statements)

References 66 publications

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“…Anti-dsDNA antibodies can bind to a complex of native dsDNA or modified DNA that contains a thymine dimer (generated during DNA photodamage). The chemically modified dsDNA may acquire a higher affinity for autoantibodies and form more stable complexes (29). Otherwise, antibodies can react with many non-DNA antigens in target cells and tissues: annexin II, α-actinin, laminin, collagen III, collagen IV, entactin, complement receptor type 1 (C1q), N-methyl-d-aspartate receptor (NMDAR), ribosomal P proteins, heparan sulfate, and others (30–39) (Table 1).…”

Section: The Origin Of Anti-dsdna Antibodiesmentioning

confidence: 99%

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

2019

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Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.

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Section: The Origin Of Anti-dsdna Antibodiesmentioning

confidence: 99%

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

2019

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“…In addition, authors have also reported that anti-dsDNA can bind to many cell types in the renal tissues—including cultured mesangial cells, podocytes, vascular endothelial cells, and proximal tubular epithelial cells—to induce cell proliferation, apoptosis, and enhanced gene/protein expression for inflammation/fibrosis [ 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. It is equally interesting that anti-dsDNA antibodies can recognize diverse DNA structures, such as single-stranded DNA, Z-form DNA, bent or elongated dsDNA, DNA-RNA hybrids, peptide-nucleic acid hybrids, and locked-nucleic acids (LNA) [ 88 , 89 , 90 ]. Accordingly, anti-dsDNA antibodies can bind to a complex of native dsDNA or modified DNA containing the thymine dimer.…”

Section: Recent Advances In the Pathophysiologic Mechanisms For Lnmentioning

confidence: 99%

Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis

Tsai

Shen

et al. 2023

IJMS

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Lupus nephritis (LN) is one of the most severe complications in patients with systemic lupus erythematosus (SLE). Traditionally, LN is regarded as an immune complex (IC) deposition disease led by dsDNA–anti-dsDNA-complement interactions in the subendothelial and/or subepithelial basement membrane of glomeruli to cause inflammation. The activated complements in the IC act as chemoattractants to chemically attract both innate and adaptive immune cells to the kidney tissues, causing inflammatory reactions. However, recent investigations have unveiled that not only the infiltrating immune-related cells, but resident kidney cells, including glomerular mesangial cells, podocytes, macrophage-like cells, tubular epithelial cells and endothelial cells, may also actively participate in the inflammatory and immunological reactions in the kidney. Furthermore, the adaptive immune cells that are infiltrated are genetically restricted to autoimmune predilection. The autoantibodies commonly found in SLE, including anti-dsDNA, are cross-reacting with not only a broad spectrum of chromatin substances, but also extracellular matrix components, including α-actinin, annexin II, laminin, collagen III and IV, and heparan sulfate proteoglycan. Besides, the glycosylation on the Fab portion of IgG anti-dsDNA antibodies can also affect the pathogenic properties of the autoantibodies in that α-2,6-sialylation alleviates, whereas fucosylation aggravates their nephritogenic activity. Some of the coexisting autoantibodies, including anti-cardiolipin, anti-C1q, anti-ribosomal P autoantibodies, may also enhance the pathogenic role of anti-dsDNA antibodies. In clinical practice, the identification of useful biomarkers for diagnosing, monitoring, and following up on LN is quite important for its treatments. The development of a more specific therapeutic strategy to target the pathogenic factors of LN is also critical. We will discuss these issues in detail in the present article.

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“…Thus, in addition to anti-DNA autoantibodies being crucial for the diagnosis of SLE they are promising targets for therapy 4 . However, in spite of growing knowledge on anti-DNAs, there is still a lack of methods for their specific detection 5 .…”

Section: Introductionmentioning

confidence: 99%

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

Domljanovic

Carstens

Okholm

et al. 2017

Sci Rep

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To date, there are multiple assays developed that detect and quantify antibodies in biofluids. Nevertheless, there is still a lack of simple approaches that specifically detect autoimmune antibodies to double-stranded DNA. Herein we investigate the potential of novel nucleic acid complexes as targets for these antibodies. This is done in a simple, rapid and specific immunofluorescence assay. Specifically, employing 3D nanostructures (DNA origami), we present a new approach in the detection and study of human antibodies to DNA. We demonstrate the detection of anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We tested the most potent non-covalent pairs of DNA and fluorescent dyes. Several complexes showed specific recognition of autoimmune antibodies in human samples of lupus patients using a simple one-step immunofluorescence method. This makes the novel assay developed herein a promising tool for research and point-of-care monitoring of anti-DNA antibodies. Using this method, we for the first time experimentally confirm that the disease-specific autoimmune antibodies are sensitive to the 3D structure of nucleic acids and not only to the nucleotide sequence, as was previously thought.

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An anti-DNA antibody prefers damaged dsDNA over native

Cited by 7 publications

References 66 publications

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies

Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis

Complexes of DNA with fluorescent dyes are effective reagents for detection of autoimmune antibodies

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