Autoimmunity to nucleosomes related to viral infection: a focus on hapten-carrier complex formation

Ghelue, Marijke Van; Moens, Ugo; Bendiksen, Signy; Rekvig, Ole Petter

doi:10.1016/s0896-8411(02)00110-5

Cited by 54 publications

(38 citation statements)

References 106 publications

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“…One has an element of foreign antigen involvement, such as infectiousrelated DNA or infectious-related immunogenic DNAbinding proteins, while the alternative involves stimulation of the immune system by true autologous chromatin. In the former, the anti-dsDNA antibody response will last predictively for the time of active infection [16,34], and therefore is predicted to be transient in its nature. Conversely, in the situation where both B cell and T cell tolerance for chromatin is terminated, true autoimmune anti-dsDNA antibody production may be similar to a sustained affinity-maturated immune response [35,36].…”

Section: The Genesis Of Anti-dsdna Antibodies In Vivo: An Infectious mentioning

confidence: 99%

Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks

Rekvig

2014

Clinical and Experimental Immunology

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Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks OTHER ARTICLES PUBLISHED IN THIS SERIESDying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16 SummaryAntibodies to mammalian dsDNA have, for decades, been linked to systemic lupus erythematosus (SLE) and particularly to its most serious complication, lupus nephritis. This canonical view derives from studies on its strong association with disease. The dogma was particularly settled when the antibody was included in the classification criteria for SLE that developed during the 1970s, most prominently in the 1982 American College of Rheumatology (ACR), and recently in The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. There are several problems to be discussed before the anti-dsDNA antibody can be accepted without further distinction as a criterion to classify SLE. Old and contemporary knowledge make it clear that an anti-dsDNA antibody is not a unifying term. It embraces antibodies with a wide spectrum of fine molecular specificities, antibodies that are produced transiently in context of infections and persistently in the context of true autoimmunity, and also includes anti-dsDNA antibodies that have the potential to bind chromatin (accessible DNA structures) and not (specificity for DNA structures that are embedded in chromatin and therefore unaccessible for the antibodies). This critical review summarizes this knowledge and questions whether or not an anti-dsDNA antibody, as simply that, can be used to classify SLE.

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Section: The Genesis Of Anti-dsdna Antibodies In Vivo: An Infectious mentioning

confidence: 99%

Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks

Rekvig

2014

Clinical and Experimental Immunology

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“…Increased levels of circulating nucleosomes are found in patients with SLE [11]. Nucleosomes are more strongly antigenic compared to DNA or histones alone [12], and become immunogenic when massively released from necrotic or apoptotic cells [13,14], and/or modified by non-self determinants [15]. In this way they stimulate the production of antibodies initially to nucleosomes and then to DNA and histones [16], and could promote tissue damage, particularly nephritis, by mediating DNA or nucleosome-specific antibody binding to basement membrane and deposition in glomeruli [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients

Ghirardello

Doria

Zampieri

et al. 2004

Journal of Autoimmunity

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“…Central candidate structures may be pure apoptotic nucleosomes (7,8) potentially generated on background of altered chromatin degradation in context of defects in genes like those encoding DNase1 (9) or serum amyloid P (10). Alternatively, hetero-complexes of self nucleosomes and nonself DNA-binding proteins derived from bacteria or viruses may account for anti-DNA or antinucleosome Ab production (6,11).…”

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confidence: 99%

Autoimmunity to DNA and Nucleosomes in Binary Tetracycline-Regulated Polyomavirus T-Ag Transgenic Mice

Bendiksen

Ghelue

Winkler

et al. 2004

The Journal of Immunology

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The mechanism(s) responsible for autoimmunity to DNA and nucleosomes in SLE is largely unknown. We have demonstrated that nucleosome-polyomavirus T-Ag complexes, formed in context of productive polyomavirus infection, activate dsDNA-specific B cells and nucleosome-specific CD4+ T cells. To investigate whether de novo expressed T-Ag is able to terminate nucleosome-specific T cell tolerance and to maintain anti-dsDNA Ab production in nonautoimmune mice, we developed two binary transgenic mouse variants in which expression of SV40 large T-Ag is controlled by tetracycline, MUP tTA/T-Ag (tet-off), and CMV rtTA/T-Ag (tet-on) mice. Data demonstrate that MUP tTA/T-Ag mice, but not CMV rtTA/T-Ag mice, are tightly controlling T-Ag expression. In MUP tTA/T-Ag transgenic mice, postnatal T-Ag expression activated CD8+ T cells but not DNA-specific B cells, while immunization with T-Ag and nucleosome-T-Ag-complexes before T-Ag expression resulted in elevated and remarkably stable titers of anti-T-Ag and anti-dsDNA Abs and activation of T-Ag-specific CD4+ T cells. Immunization of nonexpressing MUP tTA/T-Ag mice resulted in transient anti-T-Ag and anti-dsDNA Abs. This system reveals that a de novo expressed DNA-binding quasi-autoantigen maintain anti-dsDNA Abs and CD4+ T cell activation once initiated by immunization, demonstrating direct impact of a single in vivo expressed molecule on sustained autoimmunity to DNA and nucleosomes.

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Autoimmunity to nucleosomes related to viral infection: a focus on hapten-carrier complex formation

Cited by 54 publications

References 106 publications

Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks

Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks

Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients

Autoimmunity to DNA and Nucleosomes in Binary Tetracycline-Regulated Polyomavirus T-Ag Transgenic Mice

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