Antibodies to DNA. A perspective

Emlen, Woodruff; Pisetsky, David S.; Taylor, Ronald P.

doi:10.1002/art.1780291201

Cited by 96 publications

(30 citation statements)

References 73 publications

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“…Since conventional anti-DNA assays are rarely positive with sera of NHS or patients with other inflammatory diseases, anti-DNA have been considered virtually pathognomonic of SLE and a criterion in the classification of patients with SLE. These studies, however, were based on assays with very few DNA (including human, calf thymus, Escherichia coli and Crithidia luciliae), on the assumption that DNA are antigenically uniform because of the presence of conserved backbone determinants [14]. In our studies, NHS had low binding to E.…”

Section: Discussionmentioning

confidence: 79%

“…These antibodies display the IgG2 subclass and differ in specificity and immunochemical properties from both anti-DNA autoantibodies found in SLE sera as well as naturally occurring autoantibodies that have also been described in NHS. Natural autoantibodies are IgM and bind DNA, among other antigens, at low avidity [14]. In contrast, antibodies to bacterial DNA are highly selective in their binding and have high avidity [15].…”

Section: Discussionmentioning

confidence: 99%

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Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE)

Drayton

Pisetsky

1997

Clinical and Experimental Immunology

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SUMMARYTo elucidate the mechanisms of anti-DNA production, we assessed the binding of sera of normal human subjects (NHS) and patients with SLE to a panel of bacterial and mammalian DNA. Using singlestranded DNA as antigens in an ELISA, NHS showed significant binding to some but not all bacterial DNA, while lacking reactivity to calf thymus DNA. Among bacterial DNA, the highest levels of binding were observed with DNA from Micrococcus lysodeikticus and Staphylococcus aureus. In contrast, SLE sera showed high levels of binding to all DNA tested. To evaluate further immunochemical properties of the anti-DNA antibodies, the subclass distribution of these responses was evaluated by subclass-specific reagents. While NHS showed a predominance of IgG2 antibodies to bacterial DNA, SLE sera had a predominance of IgG1 antibodies to these antigens. Together, these results provide further evidence for the antigenicity of bacterial DNA and suggest that NHS and SLE anti-DNA differ in the patterns of epitope recognition as well as mechanisms of induction.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE)

Drayton

Pisetsky

1997

Clinical and Experimental Immunology

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“…The demonstration of anti-DNA antibodies in pathologic tissues, the correlation between their levels in serum and disease activity, and their high prevalence, suggest that anti-DNA antibodies participate in the pathogenesis of SLE [1,2]. Tissue deposition of DNA-anti-DNA immune complexes has been regarded as a prerequisite in disease pathogenesis [3,4].…”

Section: Introductionmentioning

confidence: 99%

Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial functional alterations

Chan

Tsang

et al. 1995

Clinical and Experimental Immunology

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SUMMARY Polyclonal anti‐dsDNA and anti‐ssDNA antibodies (PoAb) that showed significant binding to human umbilical vein endothelial cells (HUVEC) were isolated from eight patients with systemic lupus erythematosus (SLE). Anti‐dsDNA PoAbs from five patients and anti‐ssDNA PoAbs from seven patients demonstrated enhanced binding to HUVEC during active disease, compared with PoAbs obtained from corresponding patients during remission. Reduction of the DNA content in the PoAb preparations by DNase treatment was associated with enhanced binding to HUVEC in 20 of 32 PoAbs tested, which included 75%‘active disease’ PoAbs, and with reduced binding to HUVEC in three of 32 PoAbs tested, all obtained during remission. Such altered endothelial cell binding was reversed with DNA reconstitution. Binding of the remaining nine PoAbs to HUVEC was not altered by variations in their DNA content. Induced plasma membrane expression of E‐selectin, but reduced expression of vascular cell adhesion molecule‐1 (VCAM‐1) by HUVEC, was observed following incubation of HUVEC with ‘active disease’ PoAbs from three and two of the eight patients, respectively. PoAbs and serum samples from two of the eight patients during active disease induced von Willebrand factor release from HUVEC, which was not observed during remission. We conclude that anti‐DNA antibodies from selected patients with SLE can bind to endothelial cells. Correlation between cellular binding and disease activity suggests that such binding of anti‐DNA antibodies to endothelial cells could be of pathogenic significance. Preliminary data also suggest that the expression of adhesion molecules and haemostatic factor(s) by endothelial cells may be modified following their binding by anti‐DNA antibodies.

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“…For example, levels of antibodies to doublestranded (ds) DNA have been shown to fluctuate dramatically in some patients with SLE, typically in association with active renal disease (25). Temporal shifts from Sm to (U1) RNP patterns of reactivity also have been described (26), suggesting that at least some ANA specificities may emerge or change during the disease course.…”

Section: Introductionmentioning

confidence: 99%

Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

Clair

Burch²,

Ward³

et al. 1990

J. Clin. Invest.

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Antibodies to DNA. A perspective

Cited by 96 publications

References 73 publications

Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE)

Specificity and immunochemical properties of antibodies to bacterial DNA in sera of normal human subjects and patients with systemic lupus erythematosus (SLE)

Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial functional alterations

Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

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