Abstract
Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens. These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.
MeSH terms
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Adolescent
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Alleles
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Animals
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Antibodies, Antinuclear / blood
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Autoantibodies / blood
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B-Lymphocytes / enzymology
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DNA Mutational Analysis
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Deoxyribonuclease I / blood
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Deoxyribonuclease I / genetics*
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Disease Progression
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Enzyme Activation / genetics
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Female
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Heterozygote
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Humans
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Immunoglobulin G / blood
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Lupus Erythematosus, Systemic / complications
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Lupus Erythematosus, Systemic / diagnosis
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Lupus Erythematosus, Systemic / genetics*
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Mice
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Mutation
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Nucleosomes / immunology
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Polymorphism, Genetic
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Sjogren's Syndrome / blood
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Sjogren's Syndrome / complications
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Sjogren's Syndrome / diagnosis
Substances
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Antibodies, Antinuclear
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Autoantibodies
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Immunoglobulin G
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Nucleosomes
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Deoxyribonuclease I