Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.
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PMID:In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. 0 78

Sera and 5% PEG-precipitates from 20 patients with IMN, 18 with MPGN, 20 with SLE, 8 with anti-GBM disease and 17 with other varieties of glomerulonephritides, 19 patients with chronic liver or intestinal diseases, as well as those from 40 healthy adults, were tested by gel prcipitation for the presence of a ubiquitous tissue antigen (UTA) and/or its corresponding antibody, previously shown to be associated with renal disorders. The antigen was detected in sera of 5 patients with IMN, one with anit-GBM disease and one with SLE. Corresponding antibodies were present in sera of 2 patients with IMN. In 4 of 5 patients with IMN and UTA was only detected if the sera were first treated with PEG (mol. wt. 6,000) which induces precipitation of antigen-antibody complexes and other high molecular weight components in serum. The UTA was not detected in renal glomeruli by immunofluorescence. The possible significance of these findings in the pathogenesis of renal diseases is discussed.
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PMID:A ubiquitous tissue antigen and its corresponding antibody in sera of patients with glomerulonephritides. 82 47

This study demonstrates that in systemic lupus erythematosus (SLE), the presence of immune complexes on the glomerular basement membrane (GEM) does not invariabley result in histological and/or functional lesions of the kidney. Among a group of 29 lupus patients, six subjects were selected for thorough investigation, because their renal function was normal or only slightly altered though they had suffered from SLE for 20 months to 18 years. All patients had antinuclear factor, anti-native-DNA antibody and a low level of complement; 3 had anti-denatured-DNA antibody, 2 had denatured DNA-anti-denatured-DNA circulating complexes and 3 had anti-RNA-protein antibody. Kidney biopsies disclosed either no histological lesion or minimal changes in five of them and diffuse proliferative glomerulonephritis in one. By contrast, using the immunofluorescent technique, granular deposits containing the third component of complement (C3) were found on the GBM of all patients; IgG was present in 5 cases, IgM in 3, fibrinogen in two cases and around the tubules of one. Electron microscopy confirmed the presence of subendothelial and mesangial deposits. Our results also showed a good correlation between the importance of deposits and the presence of denatured DNA-anti-denatured-DNA circulating complexes. From the data obtained in these 6 cases as well as in the 23 other patients of the group, 3 categories of lupus patients could be distinguished with regard to kidney involvement: 1) patients with insignificant histological lesions, no immune deposits and essentially normal function; 2) patients with definite histological lesions, immune deposits and renal insufficiency and 3) patients with few if any histological lesions and little functional impairment contrasting with important immune deposits. The resistance of some patients to the mephrotoxic effects of immune deposits shows that lupus nephritis depends on intricate pathogenic mechanisms and suggests that these are possible antagonized by "protective" factors.
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PMID:Immune complex deposits in systemic lupus erythematosus kidney without histological or functional alterations. 114 88

To study the participation of the antibody avidity in the pathogenesis of lupus nephritis, we measured the antibody avidity to native DNA by the method of Minden and Farr (14) in patients with SLE. The avidity to native DNA was almost less than 40%. The avidity and the histological activity of lupus nephritis were well correlated; the antibody avidity of the active-group sera was higher than that of the inactive-group sera and the group without nephritis. In the group with antibodies of relatively high avidity, the complexes were deposited mainly in the subendothelial side of GBM and in the mesangium. On the other hand, in the group with low-avidity antibodies, the complexes were localized in the subepithelial side of GBM. On investigating the quality of the complexes, we noted that the complexes composed of high-avidity antibodies prepared in vitro were larger than those of low avidity and the former were larger than 19S. If the native-DNA-anti-native DNA system is the mechanism basic to lupus nephritis, the differences in immune response of the host, namely the degree of antibody avidity may greatly affect complex formation and influence the histological activity and nephritogenicity of lupus nephritis.
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PMID:Antibody avidity for native DNA in lupus nephritis. 123

The diagnostic potential of assays detecting anti-neutrophil cytoplasm antibodies (ANCA), anti-GBM antibodies and anti-dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c- and p-ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa-granule extract, proteinase-3, myeloperoxidase (MPO), elastase and lactoferrin. C-ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66-74% being c-ANCA positive. P-ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti-dsDNA positive patients constituted 57% of the 44 ANA-positive patients with systemic lupus erythematosus. It is concluded that the IIF and ELISAs for anti-proteinase-3, anti-MPO, anti-dsDNA and anti-GBM have an acceptable performance and are useful in the primary diagnostic work-up of patients suspected for secondary GN as the majority of such patients will be classified by these assays.
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PMID:Anti-neutrophil cytoplasm antibodies, anti-GBM antibodies and anti-dsDNA antibodies in glomerulonephritis. 147 49

Authors studied the dispersion of immunoreactive HSPG with monoclonal antibody specific to protein nucleus of HSPG in renal diseases associated with nephrosis syndrome. Their results showed that the dispersion of HSPG in GBM does not fully agree with dispersion of anion linkage places known in literature. In membrane and diffuse proliferative lupus glomerulonephritis immunoreactive HSPG cannot be demonstrated in the place of immune deposits, concurrent with dispersion of anion places, while it appears in GBM newly developed round the deposits. Inconsistent with this, in glomerulonephritis having minimal changes, the anion loss of GBM is not associated with absence of nuclear protein, the immunoreactive HSPG remains intact. These observations reflected in literature indicate that--similarly to proteinuria--presumably, deficiency of anion linkage places of GBM is caused by different pathomechanisms.
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PMID:[Heparan sulfate proteoglycan distribution in the glomerular basal membrane in human glomerulonephritis]. 253 43

The diagnosis of recurrent renal disease after transplantation is dependent on an accurate and complete diagnosis of the initial cause of renal failure and a similar determination of the cause of graft failure. To be classified as recurrent, the disease in the renal graft must be identical to that seen in the native kidneys. Recurrence of disease accounts for less than 2% of all graft failures, but the overall incidence of recurrent disease is probably 5 to 10 times more common. The most frequent cause of recurrent disease is glomerulonephritis, which was first recognized to recur soon after renal transplantation was introduced. It was then recognized that a variety of metabolic disorders would recur, but it has taken 25 years of experience for a clear picture to emerge of recurrence in most conditions. No initial cause of renal failure poses a contraindication to at least one attempt at transplantation, although with Fabry's disease and oxalosis, a special assessment of the risks for the individual recipient is warranted. In some patients, experience has shown the need for a delay in the commitment to transplantation (eg, in those with anti-glomerular basement membrane [GBM] antibody glomerulonephritis or Henoch Schonlein purpura), the need for the choice of a particular immunosuppressive regimen (eg, in hemolytic uremic syndrome [HUS]), the need for avoidance of primary nonfunction (eg, in oxalosis), and the desirability of avoiding live kidney donation (eg, in heterozygote donors in Fabry's disease, high-risk recipients with focal glomerulosclerosis, and in recipients with HUS). Probably all types of glomerulonephritis recur, but with great variation in frequency and severity. In some forms of glomerulonephritis, recurrence may be frequent and definite on histopathological criteria but may only have a minor clinical expression (eg, dense deposit disease, anti-GBM antibody glomerulonephritis, IgA nephropathy), but in others, recurrence is less predictable yet it is clearly associated with premature graft failure (eg, focal glomerulosclerosis, membranous nephropathy). A common theme emerging is that where the initial glomerulonephritis is aggressive and causes kidney failure over a short time, recurrence is more likely, and when present, it will lead to graft failure with an increased frequency. Clinical manifestations, the frequency of recurrence, and the prognosis of the graft are now identified for most conditions. Unexpected observations have included the rarity of recurrent systemic lupus erythematosus (SLE), the immediate return of heavy proteinuria in focal glomerulosclerosis, and the predictable return of dense deposit disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recurrence of disease following renal transplantation. 304 3

The distribution of human IgG subclasses among the glomerular deposits of 53 patients with glomerulonephritis was examined by immunofluorescence (IF) with subclass-specific monoclonal antibodies (Mab). A subclass restriction was observed in idiopathic membranous nephropathy (MN) with glomerular deposits predominantly containing IgG4 (81% of the studied biopsies) and IgG1 (75%). In de novo MN, occurring after transplantation, the restriction was markedly different, with a predominance of IgG1 (100%) and IgG2 (69%). In anti-glomerular basement membrane (a-GBM) nephritis the restriction was considerable with deposits containing almost exclusively IgG1 (91%) and IgG4 (73%). The same restriction was observed for circulating anti-GBM antibodies detected by indirect IF assay. By contrast IgG1, IgG2, and IgG3 deposits were identified in lupus proliferative glomerulonephritis. Serum IgG subclass levels were measured in 29 patients with idiopathic MN and a-GBM nephritis by an indirect competitive immunoenzymatic assay using Mab. Mean percentage of IgG2 serum level was significantly lower in patients. In spite of high variations from patient to patient, a serum IgG subclass imbalance was clearly present in 10 cases with low IgG2 and high IgG1 and IgG3 levels. The imbalance in these patients was not due to urinary loss since it was observed with a similar frequency in hypo- and normoimmunoglobulinemic patients. In 5 out of these 10 patients IgG2 levels were very low, analogous to those observed in selective IgG2 deficiency. Whether the important subclass restriction of glomerular IgG (in which patterns differed according to the type of glomerulonephritis) and the serum subclass imbalances were due to a clonally restricted antibody response to a particular antigen or to a host immune response defect, or both, remains to be elucidated.
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PMID:Glomerular and serum immunoglobulin G subclasses in membranous nephropathy and anti-glomerular basement membrane nephritis. 327 18

In summary, evidence exists that immunologically mediated renal diseases can be modulated by interfering with the mechanism of production of autoantibodies by specific antiidiotypic immunity. However, more studies are necessary to establish efficient and safe parameters from which to suggest such treatment in human immune nephritides. Although the evidence is still circumstantial, it is necessary to keep in mind that antiidiotypic antibodies may also add to glomerular immune deposits and potentially could contribute to the chronicity of some forms of immunologic nephritis. The fate of the majority of immunologic nephritides is a slow progression toward end-stage renal insufficiency. Although in most cases the etiology remains to be determined, it is generally felt that a better understanding of the initial immune dysregulation may lead to a greater possibility of control and cure. In this perspective, new directions of research, such as the one reviewed here, should be considered. Modulation of the damaging autoimmune responses in SLE or Goodpasture's Syndrome might be possible. For instance, the identification of a cross-reacting idiotype among anti-GBM antibodies would be the first step for a possible future use of natural or synthetic idiotypes for autovaccination purposes. Antiidiotype antibodies, particularly in the form of monoclonal chimaeric (mouse/human) hybridomas, could be utilized for passive immunosuppression, particularly in combination with plasmapheresis, with or without conventional immunosuppressive drugs. Clearly, this is part of a long-term process that may or may not be realized. The success of new forms of specific immunologic treatment for kidney diseases may ultimately depend upon ongoing efforts in the study of the new molecular aspects of regulation of potential nephritogenic immune responses.
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PMID:A role for antiidiotypic antibodies in immunologically mediated nephritis. 352 Dec 65

Components were solubilized from human glomerular basement membrane by digestion with collagenase and pepsin or by extraction with guanidine-HCl either directly or after previous digestion with the enzyme. The diverse preparations were used as antigens in the enzyme-linked immunosorbent assay (ELISA) of antibody titers in sera from patients with Goodpasture syndrome and patients with other forms of glomerulonephritis, that is, systemic lupus erythematosus, periarteritis nodosa, and IgA-related nephropathy. Patients with Goodpasture syndrome had high titers of IgG antibodies reacting most strongly with collagenase digests. The antigen(s) was only partly solubilized by guanidine-HCl extraction, was destroyed by pepsin digestion as well as reduction, and partly destroyed by trypsin digestion. The antigen(s) is most likely noncollagenous protein. Antibodies from patients with other forms of nephritis were directed primarily against antigens in guanidine-HCl extracts, while the antigen(s) was not solubilized by collagenase digestion. Pepsin digestion destroyed the antigen(s). The antibodies were of a different class, that is, the patients with systemic lupus erythematosus had IgG and IgA as well as IgM antibodies; the patients with periarteritis nodosa had IgM or IgG and IgA antibodies, while the patients with IgA-related nephritis had the highest recorded titers of IgA but also had IgG as well as IgM antibodies. None of the patients had antibodies directed against triple helical collagen. The antibody response in anti-GBM antibody-related nephritis, then, is different both with respect to antigen and antibody class and depends on the underlying disease syndrome.
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PMID:Antiglomerular basement membrane antibody: antibody specificity in different forms of glomerulonephritis. 613 25


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