The prognostic and therapeutic implications of DNA:Anti-DNA immune complexes in systemic lupus erythematosus (SLE)

Bardana, Emil J.; Harbeck, Ronald J.; Hoffman, Andree A.; Pirofsky, Bernard; Carr, Ronald I.

doi:10.1016/0002-9343(75)90259-4

Cited by 59 publications

(25 citation statements)

References 33 publications

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“…Polynucleotide immune complexes, chiefly involving antibody to sDNA and nDNA, are highly enriched relative to serum levels in acid buffer or deoxyribonuclease eluates of isolated glomeruli from severely nephritic kidneys of patients with SLE (5,(7)(8)(9) and in serum cryoprecipitates (10). Additional evidence for the presence of complexes of DNA and anti-DNA in the cir-culation derives from the demonstration of increased anti-DNA activity after digestion of serum with deoxyribonuclease (11,12).…”

Section: Introductionmentioning

confidence: 99%

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Winfield¹,

Faiferman²,

Koffler³

1977

J. Clin. Invest.

388

181

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Section: Introductionmentioning

confidence: 99%

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Winfield¹,

Faiferman²,

Koffler³

1977

J. Clin. Invest.

388

181

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“…T he disposal of apoptotic debris is initiated by membrane changes that facilitate the binding of IgM antibodies, acute phase proteins (C-reactive protein, CRP), and other serum opsonins to enhance phagocytosis (1,2). The disposal of apoptotic debris is crucial to immune homeostasis because the accumulation of apoptotic debris (3)(4)(5), and the formation of immune complexes (ICs) (6), have long been associated with systemic lupus erythematosus (SLE). Similarly, impaired clearance of apoptotic bodies in mice lacking scavenger receptors and complement proteins induces spontaneous autoimmunity (7,8).…”

mentioning

confidence: 99%

Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus

Monteith

Kang

Scott

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Defects in clearing apoptotic debris disrupt tissue and immunological homeostasis, leading to autoimmune and inflammatory diseases. Herein, we report that macrophages from lupus-prone MRL/lpr mice have impaired lysosomal maturation, resulting in heightened ROS production and attenuated lysosomal acidification. Impaired lysosomal maturation diminishes the ability of lysosomes to degrade apoptotic debris contained within IgG-immune complexes (IgG-ICs) and promotes recycling and the accumulation of nuclear self-antigens at the membrane 72 h after internalization. Diminished degradation of IgG-ICs prolongs the intracellular residency of nucleic acids, leading to the activation of Toll-like receptors. It also promotes phagosomal membrane permeabilization, allowing dsDNA and IgG to leak into the cytosol and activate AIM2 and TRIM21. Collectively, these events promote the accumulation of nuclear antigens and activate innate sensors that drive IFNα production and heightened cell death. These data identify a previously unidentified defect in lysosomal maturation that provides a mechanism for the chronic activation of intracellular innate sensors in systemic lupus erythematosus.

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“…A potential role of immune complexes, which have been detected in SLE sera (1)(2)(3)(4), in the development of the inflammatory process in this disease has been emphasized (5)(6)(7). In view of the important role of polymorphonuclear neutrophils (PMN) in the pathogenesis of well established immune complex diseases such as experimental serum sickness (8), it was desirable to investigate possible abnormalities of PMN function in SLE.…”

mentioning

confidence: 99%

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Hashimoto

Ziff

Hurd

1982

Arthritis & Rheumatism

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The ability of sera from patients with systemic lupus erythematosus (SLE) and Felty's syndrome to induce increased adhesiveness of normal human neutrophils (PMN) was investigated. PMN from normal healthy donors were incubated in sera from 19 patients with active SLE, 12 with inactive SLE, 20 with Felty's, 24 with rheumatoid arthritis, and 34 normal persons. After incubation, the degree of adherence of the PMN to human endothelial cells in culture, their aggregation, and superoxide (O2‐) generation were determined. Sera from patients with both active SLE and Felty's syndrome induced significantly increased PMN adherence to endothelial cells and PMN aggregation in vitro, compared with normal sera. This increased adherence to endothelial cells was maintained after heat treatment (56°C for 30 minutes) of the sera. In O2‐ generation experiments, sera from patients with active SLE induced significantly increased O2‐ release from normal PMN using both fresh and heat‐treated sera. Sera from Felty's patients demonstrated the same effect with heattreated sera but not with fresh sera. When sera from patients with active SLE and Felty's syndrome were used, all three parameters correlated significantly with each other in individual patients. In contrast, sera from the 12 patients with inactive SLE and 24 rheumatoid arthritis patients without Felty's failed to induce significant differences in the three parameters studied when compared with 34 normal controls. Fractionation of 3 SLE sera and 1 Felty's serum on Sephadex G‐200 demonstrated that the adherence enhancing factor was present in both IgG and IgG‐excluded fractions. The observed increased adhesiveness of PMN induced by SLE and Felty's sera may, at least in part, contribute to the neutropenia which is common in these diseases. Increased O2‐ release associated with PMN adherence may contribute to endothelial cell damage and vascular injury, which is also a common manifestation of these diseases.

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The prognostic and therapeutic implications of DNA:Anti-DNA immune complexes in systemic lupus erythematosus (SLE)

Cited by 59 publications

References 33 publications

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.

Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

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