Serum DNA binding activity in healthy subjects and in rheumatic disease

Hasselbacher, Peter; LeRoy, E. Carwile

doi:10.1002/art.1780170110

Cited by 61 publications

(19 citation statements)

References 12 publications

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“…In addition, recent reports have suggested that anti-DNA antibody might be found not only in SLE, but also in patients with other collagen diseases (3), as well as in normals (4). Hence, it seems imperative to clearly establish whether free DNA may be found in the normal circulation, or whether it appears only in conjunction with pathological states.…”

Section: Introductionmentioning

confidence: 99%

Free DNA in serum and plasma from normal adults.

Steinman¹

1975

J. Clin. Invest.

158

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A B S T R A C T Circulating DNA has been associated with several human disorders, including the nephritis of systemic lupus erythematosus (SLE), in which it is thought to play an etiological role. However, it remains unclear whether its appearance in the circulation is truly pathological. Several reports, each generally based on a single assay method, have disagreed as to whether DNA may circulate in normals. Some, but not all, of this disagreement may be explained by the recently described appearance of DNA in serum, but not plasma, apparently as the result of release from leukocytes in vitro.In the present report an attempt is made to clarify this problem. Normal plasma and serum samples were examined by four assays for DNA that were newly modified to enhance their specificity and/or sensitivity. Plasma DNA was undetectable by all four methods, the most sensitive of which could detect 0.05 tJg/ml of native DNA (nDNA) or 0.1 tg/ml of single-stranded DNA (ssDNA). Serum DNA was present in 14 of 16 samples tested in variable concentrations with an estimated mean of 1.9 ig/ml. It is concluded that the appearance of DNA in adult human plasma is a pathological event. Presumably, previous reports describing detection of DNA in normal plasma were based on the measurement of non-DNAase-sensitive interfering substances. Furthermore, it is emphasized that the use of serum in studies dependent on sensitive assays for DNA (or anti-DNA antibody) introduces an ambiguity that may be avoided by substitution of carefully collected plasma for serum.

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Section: Introductionmentioning

confidence: 99%

Free DNA in serum and plasma from normal adults.

Steinman¹

1975

J. Clin. Invest.

158

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“…Hasselbacher and Leroy have observed that this binding by normal sera of DSDNA represents a true antigen-antibody reaction (20). T h e difference in antibodies to DSDNA between normals and patients with SLE therefore appears to be quantitative (20). O n the basis of the present study in which anti-DSDNA antibodies were found in 9% of RA patients and on the observations of Johnson et al (21), who found anti-DSDNA antibodies i n 16% of RA patients, it would seem that patients with RA have levels of anti-DSDNA antibodies somewhere between those found in normals and those in patients with SLE.…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore these methods demonstrated that normal sera could bind a small amount of DSDNA. Hasselbacher and Leroy have observed that this binding by normal sera of DSDNA represents a true antigen-antibody reaction (20). T h e difference in antibodies to DSDNA between normals and patients with SLE therefore appears to be quantitative (20).…”

Section: Discussionmentioning

confidence: 98%

Antibodies to dna in patients with rheumatoid arthritis and juvenile rheumatoid arthritis

Bell

Talal

Schur

1975

Arthritis & Rheumatism

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Antibodies to double‐stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti‐DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.

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“…There has been considerable interest in defining the specificities of these antibodies, since questions have arisen whether anti-DNA assays are reliable for diagnosis and monitoring of disease activity, and whether antibodies with a particular kind of specificity may be especially significant for pathogenesis and diagnosis (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Secondary Structure in Denatured DNA is Responsible for Its Reaction with Antinative DNA Antibodies of Systemic Lupus Erythematosus Sera

Stollar¹,

Papalian²

1980

J. Clin. Invest.

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A B S T R A C T Experiments were designed to determine the basis for the strong competitive reaction of denatured DNA with systemic lupus erythematosus (SLE) antinative DNA antibodies. Secondary structure in denatured DNA was reflected in hyperchromicity upon heating and in multiphase kinetics ofits digestion by Si nuclease. Partial digestion by Si nuclease completely eliminated the ability of denatured DNA to react with antidenatured DNA antibodies, but not its ability to react with SLE sera. Sl nuclease-resistant cores were isolated from extensively digested denatured DNA. These cores had secondary structure, including some stable fold-back helical regions. The cores, from 20 to several hundred base pairs in size, competed with native DNA for binding by SLE sera. Other experiments measured reactions of denatured DNA under conditions that affected its secondary structure content. Its competitive activity decreased as temperature was increased from 00 to 37°C, whereas the activity of native DNA was not altered in this temperature range. With DNA pieces of 90-110 base pairs, native fragments were much more effective than the denatured fragments, in which stable helical structure is less likely to occur than in high molecular weight denatured DNA. Competitive assays with mononucleotides, oligonucleotides, homopolymers, and RNA-DNA hybrids also indicated that two strands of polydeoxyribonucleotide were required for optimal reactions with these SLE serum antibodies. The antibodies can measure stable helical regions in denatured DNA; they may also stabilize short helical regions that occur in an equilibrium of conformational forms.

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Serum DNA binding activity in healthy subjects and in rheumatic disease

Cited by 61 publications

References 12 publications

Free DNA in serum and plasma from normal adults.

Free DNA in serum and plasma from normal adults.

Antibodies to dna in patients with rheumatoid arthritis and juvenile rheumatoid arthritis

Secondary Structure in Denatured DNA is Responsible for Its Reaction with Antinative DNA Antibodies of Systemic Lupus Erythematosus Sera

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