A DNA-Reacting Factor in Serum of a Patient with Lupus Erythematosus Diffusus.

Ceppellini, R; Polli, E.; Celada, Franco

doi:10.3181/00379727-96-23544

Cited by 220 publications

(82 citation statements)

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“…Haserick et al [2] showed that LE cells could be formed by incubating normal bone marrow with lupus serum and Miescher & Fauconnet [3] demonstrated that the capacity of SLE sera to form LE cells could be absorbed out with cell nuclei and concluded that an antinuclear antibody produced the reaction. Thereafter, it was rapidly shown that lupus sera contained many antinuclear antibodies, including the initially surprising finding that there were antibodies to DNA itself [4][5][6]. the LE cell factor itself was found to be an antibody to native DNA-nucleoprotein (what would now be called a polynucleosome) [7].…”

Section: Introductionmentioning

confidence: 99%

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Macanović

Sinicropi²,

Shak³

et al. 1996

Clinical and Experimental Immunology

139

107

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SUMMARYThe effects of recombinant mouse DNase on a well established murine model of spontaneous SLE have been evaluated. Daily intraperitoneal injections of DNase were given to female NZB/NZW F 1 mice during the period of disease development from 4 to 7 months of age or at the height of disease activity from the age of 7 months for 3 weeks. This treatment was compared with the injections of diluent and with an immunosuppressive dose of dexamethasone. The effects of treatment were evaluated using the immunological parameters of disease activity (antinucleoprotein antibody, immune complexes, serum immunoglobulins, anti-cardiolipin antibodies), proteinuria, serum creatinine and renal histopathology (light microscopy, immunofluorescence and electron microscopy). The dose of dexamethasone used (1 mg/kg per day from the age of 4 months) was sufficient to suppress the development of lupus entirely. Treatment with DNase starting at the age of 4 months postponed the development of the disease by about 1 month and extended the period from the onset of disease to death by about 30%. Mice treated for 3 weeks during the most active phase of the disease at 7 months of age showed more dramatic effects. Proteinuria and serum creatinine were significantly reduced and renal histopathology was strikingly less severe than in the control group. Immune complexes involving DNA-containing antigens are believed to play a crucial role in the pathogenesis of SLE. DNA-nucleoprotein, even in immune complexes, can be destroyed by DNase. This enzyme therefore provides a rational way to interfere with the disease process. The results reported here encourage a trial of recombinant human DNase in human SLE and lupus nephritis.

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Section: Introductionmentioning

confidence: 99%

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Macanović

Sinicropi²,

Shak³

et al. 1996

Clinical and Experimental Immunology

139

107

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“…While antibodies against DNA in lupus patient sera were first described over 40 years ago [11], serologic changes occurring prior to SLE disease onset have remained uncharacterized. Because SLE patients are usually identified after autoimmunity has already commenced, the possibility of analyzing the early autoimmune response and subsequent changes in the progression to disease onset has been virtually nonexistent.…”

Section: Introductionmentioning

confidence: 99%

Development of Anti‐dsDNA Autoantibodies Prior to Clinical Diagnosis of Systemic Lupus Erythematosus

et al. 2001

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Anti‐double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti‐dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti‐dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the US Department of Defense serum repository. All 633 sera available from these patients were screened for anti‐dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti‐dsDNA antibodies prior to SLE diagnosis. The onset of anti‐dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti‐dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (≤ 6 months) for comparison. Fifty‐eight percent of the 26 cases developed a significant rise in anti‐dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti‐dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti‐dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, χ2=3.94, P<0.05). These data suggest that anti‐dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti‐dsDNA levels contributing to the onset of clinical illness in some patients with SLE.

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“…Anti-dsDNA autoantibodies were discovered in sera from SLE patients as early as in 1957 [131]. These autoantibodies were later found to be valuable for the diagnosis of SLE as they are rarely found in sera of healthy controls or patients with other autoimmune diseases (apart from autoimmune hepatitis), but are found in many SLE patients at least sometime during their disease course [132,133].…”

Section: Anti-dsdnamentioning

confidence: 99%

Biomarkers and mediators in systemic lupus erythematosus : IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays

Enocsson¹

2014

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which may affect multiple organ systems. Interferon alpha (IFNα) and autoantibodies that form immune complexes with nuclear antigens (ANA) are hallmarks believed to drive the disease into a vicious circle of inflammation, tissue damage, autoantigen exposure and autoantibody production.In SLE, the disease course is characterized by episodes of exacerbations alternating with remissions. In order to best treat the patient it is important to closely monitor symptoms and signs of disease activity. Because of the disease heterogeneity, no single biomarker has yet been found to reflect SLE disease activity in general, although anti-double stranded DNA (anti-dsDNA) antibodies sometimes indicate activity, primarily with renal involvement, and constitutes an item of the SLE disease activity score SLEDAI-2K. However, the method of anti-dsDNA measurement is not standardized and therefore varies between different laboratories. In many other inflammatory conditions, such as rheumatoid arthritis and during bacterial infections, the C-reactive protein (CRP) level is a good indicator of ongoing inflammation, but in SLE and during viral infections, CRP commonly fails to reflect the degree of inflammation. Both viral infections and SLE are characterized by IFNα, and we thus aimed to elucidate whether IFNα can inhibit CRP production. Further, four assays for anti-dsDNA antibody measurements were evaluated with regard to SLE disease specificity and activity, and a new potential biomarker of inflammation, the soluble urokinase plasminogen activator receptor (suPAR), was assessed in relation to disease activity and organ damage.An in vitro inhibitory effect of IFNα on CRP transcription and production was found in hepatocytes, and this was consolidated by in vivo studies of CRP and IFNα in sera from well-characterized SLE patients (KLURING; Kliniskt lupusregister i nordöstra Götaland). Here, CRP and disease activity were associated among patients without IFNα and without a CRP lowering gene variant (SNP rs1205). The poor disease activity compliance of CRP could therefore be explained, at least in part, by polymorphisms in the CRP gene and increased levels of IFNα. Critical differences between the methods measuring anti-dsDNA were found regarding disease specificity and ability to reflect disease activity and the results suggests the Crithidia luciliae immunofluorescence test (CLIFT) for diagnostic purposes and a bead-based multiplex assay (FIDIS) for monitoring of disease activity.

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A DNA-Reacting Factor in Serum of a Patient with Lupus Erythematosus Diffusus.

Cited by 220 publications

References 0 publications

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Development of Anti‐dsDNA Autoantibodies Prior to Clinical Diagnosis of Systemic Lupus Erythematosus

Biomarkers and mediators in systemic lupus erythematosus : IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays

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