DNA:Anti-DNA Complexes: Their Detection in Systemic Lupus Erythematosus Sera

Harbeck, Ronald J.; Bardana, Emil J.; Köhler, Peter F.; Carr, Ronald I.

doi:10.1172/jci107242

Cited by 172 publications

(53 citation statements)

References 11 publications

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“…A number of investigators have shown in vitro that free antibody is released from DNA-anti-DNA immune complexes by digestion with deoxyribonucleases (DNAse) (19,20). Recently, Sano and Morimoto (21) showed that immune complexes from the sera of SLE patients contained small molecular weight DNA, and other investigators (22) found that, whereas DNAse digestion decreased the size of complexes, some IgG remained bound to small DNA fragments.…”

Section: Discussionmentioning

confidence: 99%

Clearance of circulating DNA-anti-DNA immune complexes in mice.

Emlen¹,

Mannik²

1982

The Journal of Experimental Medicine

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Immune complexes composed of DNA and antibodies to DNA contribute to tissue injury in systemic lupus erythematosus (SLE) (1, 2). High titers of antibodies to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) are associated with the disease (2, 3), and antibodies to DNA have been eluted from the kidneys of SLE patients (4, 5). Direct demonstration of circulating DNA-anti-DNA immune complexes has been reported (6, 7), but not confirmed (8).Whereas the fate of circulating immun e complexes such as HSA-anti-HSA has been well characterized (9), the behavior of immune complexes containing DNA has not been studied. DNA is cleared from the circulation extremely rapidly, faster than large-latticed complexes (10). Furthermore, in vitro DNA binds to glomerular and skin basement membranes (11). These unique features of DNA might also influence the fate of immune complexes containing DNA as the antigen. In this study, immune complexes were prepared in vitro with ssDNA and antibodies to DNA from a patient with SLE. The clearance and organ localization of these immune complexes was studied in normal mice and compared with the clearance of heat aggregated immunoglobulin (IgG), serving as a model for immune complexes. Our results demonstrate that the clearance of ssDNA-anti-DNA immune complexes parallels the clearance of DNA alone and is much more rapid than the clearance of aggregated IgG. Materials and MethodsAntibodies to DNA. Serum from a patient with active SLE, kindly provided by Dr. J. V. Jones of the University of Chicago, was precipitated with 50% saturated ammonium sulphate and resuspended in borate buffer (0.2 M borate, 0.15 M NaCI; pH 8.0). This material was radiolabeled with 125I by the iodine monochloride method (12), and free 125I was removed by dialysis (final sp act 30,000 epm//~g). This preparation, containing IgM and IgG, was gel filtered over Sepharose 4B (Pharmacia Fine Chemicals, Div. of Pharmaeia Inc., Piscataway, N J) and the included IgG peak was pooled (see Figure 1 A). Reehromatography of this peak showed no excluded protein.ssDNA. Calf thymus DNA (Worthington Biochemical Corp., Freehold, N J) was heat denatured and labeled with laxI according to the method of Commerford (13). After dialysis to remove free xa'I, the DNA was passed over Sepharose 4B, and the excluded material was pooled (Fig. 1 B). Analysis of this DNA on 2% agarose gel electrophoresis revealed a mean mol wt of 640,000 with a range of 400,000-800,000.Preparation of Immune Complexes. I0 mg of 125I IgG was mixed with 20/~g of lalI ssDNA and incubated at 37°C for 30 rain. This mixture (2 ml) was gel filtered on a 50-ml Sepharose 4B column, and the 125I and 131I counts per 0.5 ml fraction were determined (Fig. 1C).

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Section: Discussionmentioning

confidence: 99%

Clearance of circulating DNA-anti-DNA immune complexes in mice.

Emlen¹,

Mannik²

1982

The Journal of Experimental Medicine

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“…[112][113][114][115] Subsequently, we will discuss the relationship between homeostatic enzymatic degradation of extracellular DNA and the development of SLE and lupus kidney dysfunction known as lupus nephritis.…”

Section: Autoimmune and Vasculitic Diseasementioning

confidence: 99%

NETosis: how vital is it?

Yipp¹,

Kubes

2013

Blood

830

793

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In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.

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“…Systemic lupus erythematosus (SLE)l is a multisystem disease characterized by the production of large quantities of antibodies reactive with self-antigens (1,2). The immune system of patients with active SLE is characterized by generalized B-cell hyperactivity (3)(4)(5)(6)(7) and impaired T-cell function (8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%