Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus.

Raptis, Leda; Ménard, Henri A.

doi:10.1172/jci109992

Cited by 157 publications

(81 citation statements)

References 30 publications

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“…Moreover, nucleosome levels were not correlated with the SLEDAI score nor with low C3 levels, a biologic marker of disease activity. Most previous work on circulating DNA antigen levels has shown an association between elevated DNA antigen levels and active disease, in particular, with central nervous system involvement and systemic vasculitis (13,17,19). Nevertheless, another study reported an absence of a statistically significant difference in plasma DNA antigen levels between SLE patients who did and…”

Section: Discussionmentioning

confidence: 93%

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus. Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity

Amoura

Piette

Chabre

et al. 1997

Arthritis & Rheumatism

167

118

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Objective. To assess nucleosome plasma levels in patients with systemic lupus erythematosus (SLE) and to study the correlations with serum antinucleosome, anti-double-stranded DNA (anti-dsDNA), and antihistone antibody activities, as well as with disease activity (by the SLE Disease Activity Index [SLEDAI]).Methods. In a cross-sectional study, we assessed 58 SLE patients for their plasma nucleosome levels. Plasma nucleosome levels as well as serum antinucleosome, anti-double-stranded DNA, and antihistone antibody activities were assessed by enzyme-linked immunosorbent assay. SLE activity was evaluated using the SLEDAI.Results. The mean (.t SD) plasma nucleosome concentration in SLE patients was 52 2 159 ng/ml (range 5-1,180), and was significantly higher than that of the controls (16 2 8.8 ng/ml, range 8-52; P = 0.03).

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Section: Discussionmentioning

confidence: 93%

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus. Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity

Amoura

Piette

Chabre

et al. 1997

Arthritis & Rheumatism

167

118

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“…In human systemic lupus erythematosis (SLE), impaired phagocytosis of apoptotic materials by macrophages has been reported [19,20], providing an explanation for increased levels of early apoptotic cells, DNA, and nucleosomes observed in the circulation of SLE patients [21][22][23][24].…”

Section: Phagocytosis Of Apoptotic Cells and Regulation Of Immune Resmentioning

confidence: 99%

Regulation of cytokine production during phagocytosis of apoptotic cells

2006

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Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic cells would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The IL-12 family of cytokines (IL-12, IL-23, and IL-27) and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells (APCs) and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro-and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein (GC-BP), through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.

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“…47,48 providing an explanation for increased levels of early apoptotic cells, DNA and nucleosomes observed in the circulation of SLE patients. [49][50][51][52] The impaired clearance of apoptotic cells resulting in an accumulation of late apoptotic and secondary necrotic cells including oligosomes might lead to an activation of autoreactive T and B cells. 44 At the genetic level, how these IL-10 promoter SNPs affect IL-10 gene expression has long evaded elucidation.…”

Section: Introductionmentioning

confidence: 99%

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by the dysregulation of T and B cells that leads to hyperactivity of B cells and production of autoantibodies, and involves both environmental and genetic factors. Interleukin-10 (IL-10) is a candidate susceptibility gene in SLE. In particular, three IL-10 promoter singlenucleotide polymorphisms (SNPs; À1082A/G, À819T/C and À592A/C) are strongly associated with the pathogenesis of SLE. We found that the homozygous GCC haplotype linked to greater SLE severity confers higher IL-10 gene transcriptional activity than the ATA haplotype in macrophages that encounter apoptotic cells, because of the differential DNA binding to the À592 SNP by a nuclear protein uniquely induced by apoptotic cells. We identified this protein as poly(ADP-ribose) polymerase-1, confirmed its physiological role and characterized its molecular properties in modulating IL-10 production during phagocytosis of apoptotic cells. This study unveils a novel direct link between DNA damage repair/apoptosis pathways and IL-10-mediated immune regulation.

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Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus.

Cited by 157 publications

References 30 publications

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus. Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus. Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity

Regulation of cytokine production during phagocytosis of apoptotic cells

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

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