Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to the proliferating cell nuclear antigen (PCNA) detected in patients with systemic lupus erythematosus (SLE) were allowed to react with a nuclear antigen expressed predominantly in proliferating cells such as cultured cells and mitogen-transformed cells. The characterization of both structure and function of PCNA has been studied. PCNA has been identified as a protein with a molecular weight of about 33 kD and isoelectric point of 4.8. The expression of PCNA increased in the cell from the late G1 and S phases of the cell cycle immediately preceding DNA synthesis. Recent studies have revealed that the auxiliary protein of DNA polymerase-d is identical to PCNA. Anti-PCNA antibodies can be detected by the methods of immunofluorescence (IF), double immunodiffusion (DID), counterimmunoelectrophoresis (CIE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB). Anti-PCNA antibodies were specifically detected in 2-5% of the patients with SLE by DID. In spite of their low frequency, anti-PCNA antibodies are useful as a clinical marker for SLE. Several reports indicated that patients with PCNA positive SLE showed a high frequency of renal and central nerve system (CNS) involvements and thrombocytopenia. In these patients, the anti-PCNA antibody titer was elevated before the development by proteinuria and the titer of anti-PCNA antibodies was decreased by treatment with corticosteroids. In addition, anti-PCNA antibodies have been known as a useful tool to detect activated lymphocytes and malignant proliferating cell.
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PMID:[Anti-PCNA antibody]. 810 8

The fine binding characteristics of three well-characterized human autoantibodies B3, RH14 (anti-DNA) and UK4 (anti-cardiolipin) in their IgG and cloned Fab formats, were investigated. Although in severe combined immunodeficiency (SCID) mice B3 and RH14 both induce proteinuria, only RH14 induces early features of lupus nephritis, whereas UK4 exhibits lupus anticoagulant activity. RH14 exhibited up to 10 fold higher binding to DNA compared to that shown by B3 or UK4 and involved significant electrostatic and phosphate group interactions. Only RH14 exhibited strong anti-Sm cross-reactivity residing on the C-terminus of the antigen as determined by the use of 76 overlapping 15mer peptides. Chain shuffling experiments indicate that anti-Sm/RNP and anti-Jo-1 activities of B3 and UK4 co-exist on one of the two chains (light, B3; heavy, UK4). The present study provides evidence that a human anti-DNA antibody can also be an anti-ENA antibody. Furthermore, the anti-DNA antibodies also exhibited cross-reactivity against glutathione-S-transferase and DNA polymerase PolIV of bacterial origin. This is the first demonstration of the presence of such cross-reactivities on lupus anti-DNA antibodies. We now demonstrate that subsets of sera from the patients with lupus, recognise these antigens. This observation may in some cases provide a mechanism for the common expression of a variety of autoantibodies observed in systemic lupus erythematosus (SLE).
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PMID:Fine binding characteristics of human autoantibodies-partial molecular characterization. 1518 28

While immunoglobulin G (IgG) antibodies to double-stranded (ds)DNA are serological markers of systemic lupus erythematosus (SLE), not all antibodies to DNA (anti-DNA) are able to cause tissue damage to a similar extent. It has been proposed that anti-DNA-induced renal damage could be linked to differences in the fine specificity of the antibodies. In an attempt to gain insight into their fine binding properties, we investigated the cross-reactivity of two human lupus monoclonal IgG anti-dsDNA (B3 and RH14) to a recently described Escherichia coli PolIV (a DNA polymerase). These autoantibodies possess distinct pathogenic properties in severe combined immunodeficient (SCID) mice. Although both antibodies cause proteinuria, only RH14 induces early histological features of lupus nephritis. Both RH14 and B3 bound PolIV; however, they exhibited a marked difference in their reactivity to the PolIV-dsDNA complex. Alhough RH14 exhibited significant activity to the complex, the binding of B3 to PolIV complexed with dsDNA was almost abolished. Furthermore, there was a significant difference in the way the lupus sera recognized naked dsDNA and that presented on PolIV. Although 67% of lupus sera bound naked dsDNA, approximately 90% of these sera (93% calf thymus DNA; 90% synthetic oligonucleotide) reacted to the complex when dsDNA was presented on PolIV. Thus, the IgG anti-dsDNA likely to exist in lupus patients may be distinguished into those that recognize dsDNA in the context of PolIV and those which do not. This difference in binding ability may help to distinguish those dsDNA antibodies that are more pathogenic.
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PMID:Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV. 1572 Apr 43