Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The performance of immunoassays for the detection of autoantibodies is of critical importance to the diagnosis and assessment of patients with systemic lupus erythematosus (SLE). Our objective was to compare 3 multiplexed assays for measurement of multiple autoantibodies and their association with global disease activity, active nephritis and cumulative organ damage in systemic lupus erythematosus (SLE). Stored sera, clinical and laboratory data from the enrollment visit of a long-term lupus registry were used. Autoantibodies were measured using the BioPlex 2200 ANA screen (Bio-Rad), QuantaPlex ENA8 (INOVA Diagnostics) and recomLine ANA/ENA (Mikrogen). The analytes included dsDNA, chromatin, ribosomal P protein, SS-A/Ro60, Ro52, SS-B/La, Sm, U1-RNP, centromere B, topoisomerase 1 and Jo-1 (histidyl tRNA synthetase). Global SLE disease activity was measured by the SLE disease activity index (SLEDAI) and cumulative organ damage by the SLICC/ACR damage index (SDI). One hundred ninety two patients (87% female; 91% Caucasian; mean disease duration 8.8years) were studied. Agreement between the 3 assays varied from 70% to 99% (Cohen's kappa: 0.04-0.88). There were significant associations between SLEDAI scores (excluding anti-dsDNA) and ANA (INOVA, Mikrogen), anti-dsDNA (Bio-Rad, Mikrogen), anti-chromatin (Bio-Rad, INOVA), anti-Ro (Mikrogen), anti-Sm and anti-U1-RNP (all 3 immunoassays) (p=0.002-0.05). Concurrent lupus nephritis was associated with anti-dsDNA (Bio-Rad (p=0.017) or Bio-Rad and Mikrogen together (p=0.015)). There was no significant association between autoantibodies and SDI scores. The overall agreement between assays for the detection of autoantibodies was reasonable. The greatest discordance (70-83%) occurred with those autoantibodies most strongly associated with global SLE disease activity (ANA, anti-dsDNA, anti-chromatin and anti-Sm). Furthermore, there were differences between assays in their associations with global SLE disease activity and lupus nephritis.
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PMID:Comparison between multiplex assays for autoantibody detection in systemic lupus erythematosus. 2043 30

Hepatitis B virus (HBV), the causative agent of chronic hepatitis B and prototypic hepadnavirus, is a small DNA virus that replicates by protein-primed reverse transcription. The product is a 3-kb relaxed circular DNA (RC-DNA) in which one strand is linked to the viral polymerase (P protein) through a tyrosyl-DNA phosphodiester bond. Upon infection, the incoming RC-DNA is converted into covalently closed circular (ccc) DNA, which serves as a viral persistence reservoir that is refractory to current anti-HBV treatments. The mechanism of cccDNA formation is unknown, but the release of P protein is one mandatory step. Structural similarities between RC-DNA and cellular topoisomerase-DNA adducts and their known repair by tyrosyl-DNA-phosphodiesterase (TDP) 1 or TDP2 suggested that HBV may usurp these enzymes for its own purpose. Here we demonstrate that human and chicken TDP2, but only the yeast ortholog of TDP1, can specifically cleave the Tyr-DNA bond in virus-adapted model substrates and release P protein from authentic HBV and duck HBV (DHBV) RC-DNA in vitro, without prior proteolysis of the large P proteins. Consistent with TPD2's having a physiological role in cccDNA formation, RNAi-mediated TDP2 depletion in human cells significantly slowed the conversion of RC-DNA to cccDNA. Ectopic TDP2 expression in the same cells restored faster conversion kinetics. These data strongly suggest that TDP2 is a first, although likely not the only, host DNA-repair factor involved in HBV cccDNA biogenesis. In addition to establishing a functional link between hepadnaviruses and DNA repair, our results open new prospects for directly targeting HBV persistence.
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PMID:Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. 2520 58