Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus.

Tan, Eng M.; Schur, Peter H.; Carr, Ronald I.; Kunkel, Henry G.

doi:10.1172/jci105479

Cited by 756 publications

(335 citation statements)

References 29 publications

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“…Circulating extracellular DNA have been detected in both healthy and sick individuals (13) and are present in large concentrations in cancer patients due to apoptosis (14)(15)(16) and active secretion (17).…”

Section: Introductionmentioning

confidence: 99%

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Hart

Patton

Jacobson

et al. 2005

J Assist Reprod Genet

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Purpose : DNA-damaging factors have been reported in patients that failed to achieve pregnancy after assisted reproductive technologies (ART). The hypothesis was that increased circulating cell-free DNA released by damaged cells could predict unfavorable conditions leading to failed ART treatment. The objective was to compare the relative concentrations of cell-free DNA in the luteal phase sera of nonpregnant versus pregnant patients. Methods : Frozen-thawed sera (30 IVF cases) were obtained 1 week after embryo transfer. There were 16 pregnant and 14 nonpregnant cases and controls consisting of male sera (n = 8 cases). Modified isocratic capillary electrophoresis was performed and the images analyzed for cell-free DNA. Results : Circulating cell-free DNA were identified in the sera of all patients. The serum concentrations of high (12 kb) and low (1 kb) molecular weight cell-free DNA were similar for both nonpregnant and pregnant patients. Male control sera had higher cell-free DNA concentrations compared with females. Evaluation of sera from a control case showed no fluctuations in cell-free DNA concentrations throughout specific days of the menstrual cycle. Conclusions : The results do not support the use of the luteal phase cell-free DNA concentration as a marker for failed pregnancies. The equal concentrations of high and low molecular weight cell-free DNA and ladder band-like gel patterns suggested cell apoptosis as the source of DNA.

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Section: Introductionmentioning

confidence: 99%

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Hart

Patton

Jacobson

et al. 2005

J Assist Reprod Genet

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“…Autoantibody formation against self antigens is one of the core features of autoimmune diseases such as Systemic Lupus Erythematosus (SLE) [1,2]. Breakdown of tolerance results in autoantibodies reacting with dsDNA and protein antigens such as small nuclear ribonucleoproteins (snRNPs, e.g.…”

Section: Introductionmentioning

confidence: 99%

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Meilof

Veldhoven

Swaak³

et al. 1997

Journal of Autoimmunity

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Autoimmune diseases such as Sjögren's Syndrome and systemic lupus erythematosus (SLE) are characterized by serum autoantibodies against protein components of small cytoplasmic ribonucleoproteins (scRNPs). The origin and regulation of these anti-Ro/SS-A and anti-La/SS-B antibodies is not well understood. Regular co-occurrence of these two autoantibodies in humans together with murine studies on antibody responses against scRNPs after immunization suggest a role for scRNPs as common antigen. We sought additional evidence for this hypothesis in a longitudinal serological study of patients with SLE. Quantitative measurement of the antibody responses against Ro/SS-A and La/SS-B proteins and for comparison to dsDNA in 852 serum samples was performed. These samples were collected from nine patients during an average observation period of more than 10 years. A significant and strong correlation between the two anti-scRNP responses emerged during 90% of follow-up. In contrast, correlation of anti-scRNP with anti-dsDNA responses was remarkably absent in the same patients. Our results confirm the unique relationship between anti-Ro/SS-A and anti-La/ SS-B responses and could thus be interpreted as support for a model wherein induction and perpetuation of autoantibody production is dependent on scRNPs containing both proteins as antigen.

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“…McCoubrey-Hoyer et al [33] reported that the serum concentration of DNA in normal people was in the range of 4-13 ng/ml, and in SLE patients in the range of 4-400 ng/ml. Tan et al [34] detected increased levels of native (ds) DNA in some lupus sera using the gel diffusion method. Lambert & Dixon [31] found circulating DNA in sera of NZB/ NZW mice.…”

mentioning

confidence: 99%

Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay

Macanović

Lachmann

1997

Clinical and Experimental Immunology

104

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SUMMARYA new radial enzyme diffusion (RED) method for the measurement of DNase activity in serum and urine is described. The sensitivity of the assay is in the range of 15 . 6-500 ng/ml. The assay is based on the hydrolysis of double-stranded (ds) DNA (or nucleosomes) in agarose. The specificity of the reaction for DNase I was established by showing that either EDTA in the reaction buffer or G-actin abolished DNase activity. Being a functional assay, RED has advantages over radioimmunoassay (RIA) or ELISA, since antigenic assays may also measure complexes of DNase with actin. This method was used to measure DNase activity in the sera and urine of lupus-prone mice (NZB/NZW F 1 hybrids, aged 4-6 weeks). Serum DNase activity in these mice was significantly lower (mean 9 ng/ml) than in control, normal mice of the same age and sex (mean 37 ng/ml). Concentration of DNase in the urine of 4-6-week-old female NZB/NZW F 1 hybrids (24 ng/ml) was significantly lower then in control mice (521 ng/ml). The RED method was used to measure the concentration of actin as the DNase inhibitor in serum. G-actin in the presence of ATP binds DNase and inhibits its nucleolytic activity. Since ATP is necessary for the actin inhibition of DNase I, this shows that there is actin as well as DNase I in the serum. Actin is not only ATP-dependent, but also heat-labile. Heating the sera for 10 min at 50ЊC increases DNase activity. This is an alternative method for measuring the concentration of actin in the serum. An almost identical estimate of actin concentration in sera of normal mice was found from the difference of DNase activity in the presence or absence of ATP (mean actin concentration ¼ 21 ng/ml) or from the difference of DNase activity in heated and non-heated serum (mean actin concentration 18 ng/ml). We were not able to demonstrate DNase inhibitors in the urine of either control or NZB/W F 1 hybrid mice.

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Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus.

Cited by 756 publications

References 29 publications

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production

Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay

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