A molecular analysis of the low serum deoxyribonuclease activity in lupus patients

Tew, Monty B.; Johnson, Randall W.; Reveille, John D.; Tan, Filemon K.

doi:10.1002/1529-0131(200110)44:10<2446::aid-art409>3.0.co;2-u

Cited by 39 publications

(33 citation statements)

References 8 publications

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“…Our observations confirm previous reports (11,26) that DNase enzyme activity is significantly decreased in the sera of SLE patients compared to those in the sera of healthy individuals.…”

Section: Discussionsupporting

confidence: 93%

“…A mutation in the second exon of the DNASE1 gene has been reported (29), but its low prevalence does not explain the decreased activity of the enzyme in most SLE patients (3,10,21,26).…”

Section: Discussionmentioning

confidence: 99%

“…Some suggest the presence (30) and others suggest the absence (11,26) of such a factor, thought to be an antibody (30).…”

Section: Discussionmentioning

confidence: 99%

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Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

Sallai¹,

Nagy²,

Dérfalvy³

et al. 2005

Clin Vaccine Immunol

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Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ؎ 12.1%) than in the controls (81.3% ؎ 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ؎ 18.2%; P ‫؍‬ 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ؎ 851) than the controls (1.44 ؎ 2.77; P < 0.01) or UCTD patients (39.9 ؎ 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide range of pathological autoantibodies. Those directed against chromatin components, e.g., double-stranded DNA (dsDNA), histones, and the nucleosome, are of paramount pathological importance (6,8,20).Recent studies of patients with SLE suggest the increasing diagnostic importance of antinucleosome antibodies, in addition to antibodies directed against dsDNA (1, 17). These circulating antibodies may form immune complexes with their target antigens, the glomerular deposition of which will lead to the development of renal damage (12,14).The incidence of immune complex-mediated glomerulonephritis (GN) among SLE patients varies from 30 to 60%. Several studies have confirmed that autoantibodies are produced through an antigen-driven T-cell-dependent mechanism (13,23,27). According to this model, the defective clearance of apoptotic cell debris predisposes individuals to SLE through the accumulation of the chromatin components arising from the dying cells (5, 28).DNase I (pancreatic DNase) and DNase II (spleen acid DNase) cleave nucleosomal DNA, which promotes the disposal of circulating nuclear material. DNase I, a glycoprotein with a molecular mass of 30,400 Da, is a cation-binding secretory endonuclease that digests dsDNA in a sequence-dependent manner (24). DNase II,...

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“…Our observations confirm previous reports (11,26) that DNase enzyme activity is significantly decreased in the sera of SLE patients compared to those in the sera of healthy individuals.…”

Section: Discussionsupporting

confidence: 93%

“…A mutation in the second exon of the DNASE1 gene has been reported (29), but its low prevalence does not explain the decreased activity of the enzyme in most SLE patients (3,10,21,26).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

Sallai¹,

Nagy²,

Dérfalvy³

et al. 2005

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Moreover, DNase I-deficient mice produced by gene targeting show the classical symptoms of SLE, which are the presence of anti-nuclear antibodies and glomerulonephritis [38]. Mutation of DNase I gene has also been found in some SLE patients [39], although not all SLE patients have defects in DNase genes [40][41][42]. Therefore, multiple factors are probably involved in causing the reduced DNase activity in SLE.…”

Section: Discussionmentioning

confidence: 99%

The uptake and degradation of DNA is impaired in macrophages and dendritic cells from NZB/W F1 mice

et al. 2005

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“…Chez la souris (NZB/W (F1), une DNAase recombinante permet de réduire le nombre de cellules splé-niques secrétant des Ac anti-ADN natif, mais ne modifie pas leur survie. Chez l'homme, les anomalies génomiques des DNAase (DNAase I) semblent rares, décrites chez moins de 10 % des patients [88][89][90]. Cependant, dans un premier travail, l'utilisation thérapeutique d'une DNAase recombinante humaine a suggéré une efficacité clinique ou biologique [91].…”

Section: L'élimination Enzymatique Des Autoantigènes (Adn) Par Les Dnunclassified

Immunothérapies du lupus systémique : innovations et perspectives

Sibilia¹,

Sordet²

2005

Revue du Rhumatisme

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A molecular analysis of the low serum deoxyribonuclease activity in lupus patients

Cited by 39 publications

References 8 publications

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

The uptake and degradation of DNA is impaired in macrophages and dendritic cells from NZB/W F1 mice

Immunothérapies du lupus systémique : innovations et perspectives

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