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)

Schizophrenia and certain forms of idiopathic mental retardation may result from covert immune complex disease of the basal lamina of the choroid plexus, a process already known to cause covert transport dysfunction in similar structures of, for example, skin, bowel, kidney, and endocrines. Plexial attack could lead to cerebrospinal fluid contamination and then, via an "open" ependyma, to neurotransmitter dysfunction in the periventricular limbic brain. The immune complex mechanism implies polygenic induction, direct or autoimmune, of immune sensitivity to exogenous agents and is thus compatible with the genetic picture in schizophrenia. Candidate agents include viral coat peptides and cereal grain glutens. The glutens are known to cause immune complex skin and bowell disease variants, and some empirical evidence links them to schizophrenia. Only newer immunofluorescence methods can detect the pathology, which is otherwise silent. Systemic lupus erythematosus provides a model since it is a genetic immune complex disease strongly associated with schizophreniform psychoses, exhibits choroid plexial immunofluorescence but no central nervous system pathology by ordinary methods, and may be triggered by viruses.
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PMID:Covert transport dysfunction in the choroid plexus as a possible cause of schizophrenia. 4 42

The level and avidity of anti-DNA antibody in the serum of New Zealand Black/White (NZB/W F1) hybrid mice has been determined. The results show that there is an age and sex-related variation in the avidity of this antibody. In mice of both sexes, the avidity of circulating anti-DNA antibody increases up to 5 months of age; thereafter the avidity falls with increasing age. These variations are more marked in males, but female mice consistently have lower avidity anti-DNA antibody than males. Thus the time of onset, time course and severity of the murine lupus syndrome in NZB/W F1 mice are associated with the presence of increasing levels of low avidity anti-DNA antibody in the serum. These results are discussed in the context of the possible role of low avidity antibody in immune complex disease.
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PMID:The role of low affinity antibody in immune complex disease. The quantity of anti-DNA antibodies in NZB/W F1 hybrid mice. 12 30

The clinical history and biological investigations of a patient presenting an immune complex disease induced by Peroben are reported. Biological signs were those of a drug-induced lupus syndrome. A provocation test allowed disclosure of its pathomechanism, since during Peroben intake a high C1q binding activity occurred and later regressed, while deposits of IgM and C3 were evidenced in the vessel walls. Complete or partial thrombosis succeeded accompanying a leukocytoclastic vasculitis.
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PMID:Immune complex disease associated with Peroben intake. 15 1

A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.
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PMID:Effect of plasma exchange on circulating immune complexes and antibody formation in patients treated with cyclophosphamide and prednisone. 93 Sep 42

The immunoglobulin class and subclass distribution of antibodies to double-stranded (ds) DNA has been determined in NZB/W F1 hybrid mice by a double antibody radioimmunoassay. The results show that there are marked age- and sex-related variations in the class and subclass distribution of these antibodies. In young mice of both sexes, the predominant anti-ds DNA antibody was of the IgM class, but as the animals aged, there was an increase in the level of the IgG2a and IgG2b antibodies. An apparent switch from predominantly IgM to IgG antibody occurred in females before males and at about the age of onset of overt immune complex disease in these animals. The possible significance of these results in the pathogenesis of the murine lupus syndrome is discussed.
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PMID:Changes in immunoglobulin class and subclass of anti-DNA antibodies with increasing age in N/ZBW F1 hybrid mice. 99 64

It has been proposed that autoimmune immune complex disease, of which SLE is the type example, is caused essentially by a failure to properly metabolise immune complexes and that this allows the establishment of feedback cycles which cause more immune complexes to be formed. The essential genetic predisposition to this disease is complement deficiency of the components of the early classical pathway and some degree of genetic complement deficiency, particularly of C4a, is found in more than half the patients. It seems likely that acquired complement deficiencies, possibly present at the time of initiation of the disease, may be important in many of the other cases.
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PMID:The Seventh K Prathap Memorial Lecture. The pathogenesis of autoimmune immune complex disease. 146 11

Platelet-activating factor (PAF) has been suggested recently to play an important role in immune glomerulonephritis, favoring the formation of immune deposits in glomeruli and contributing to the local inflammatory reaction. Here we sought to investigate whether urinary PAF excretion was modified in New Zealand Black x New Zealand White mice a model of genetically determined immune complex disease which mimics systemic lupus in humans and whether changes in PAF urinary excretion values correlated with the extent of proteinuria. To clarify the possible "in vivo" relevance of these findings we evaluated whether PAF receptor antagonist has any influence on the evolution of renal disease and survival of these mice. Our results showed that: 1) in lupus mice urinary PAF excretion increased progressively with age in New Zealand Black x White; 2) the increase in PAF excretion correlated with the severity of proteinuria; and 3) the chronic administration of a PAF receptor antagonist [L-659,989 [(+/- )-trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5- (3,4,5-trimethoxyphenyl)tetrahydrofuran]] starting from 26 weeks of age significantly delayed the onset of proteinuria and prolonged survival.
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PMID:Platelet-activating factor receptor blocking reduces proteinuria and improves survival in lupus autoimmune mice. 165 Aug 36

In this paper an overview of the present knowledge on antibodies against DNA will be presented. Diagnostic, prognostic and pathogenic aspects of anti-DNA will be highlighted. Detection of antibodies to DNA in the circulation of a patient by an assay selective for high avidity anti-DNA is highly diagnostic for SLE. Anti-DNA of low avidity occurs in rheumatic diseases other than SLE as well, making detection of such antibodies of less diagnostic value. Furthermore, data will be presented that show that the anti-DNA ELISA in its present form is not suited as a diagnostic tool. Not only disease features of SLE vary from patient to patient, anti-DNA avidity does so too. A relationship between anti-DNA avidity and clinical features can be found: high avidity anti-DNA is more abundant in patients with nephritis, low avidity anti-DNA in patients with CNS involvement. Prognostically, a steady increase of the level of high avidity anti-DNA generally heralds an upcoming exacerbation in a patient. Furthermore, 85% of the patients who do not have SLE at the time (high avidity) anti-DNA is detected in their serum, will develop the disease within the next few years. It is noteworthy, that patients with only low avidity anti-DNA in their circulation develop a more mild form of SLE; the (low) avidity of their anti-DNA seldomly increases during the course of their disease. The relevance of anti-DNA to the pathogenesis of SLE still is a matter of debate. On the one hand, the association of parameters of anti-DNA that determine the size of the complexes formed with DNA is in favour of the classical hypothesis, which states that SLE is primarily an immune complex disease. On the other hand, recent data on crossreactions of anti-DNA with phospholipids, glycosaminoglycans and other (poly-negative) structures plead for a role of such crossreactivities in the pathogenesis of SLE.
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PMID:Antibodies to DNA in patients with systemic lupus erythematosus. Their role in the diagnosis, the follow-up and the pathogenesis of the disease. 220 88

To study the role of local production of complement proteins during the evolution of a naturally occurring immune complex disease, C3, C4, C2 and Factor B mRNA expression was assessed in several tissues of the inbred mouse strains NZB and (NZB x W) F1 hybrid. In the NZB/W F1 hybrid strain, coincident with the development of glomerulonephritis a marked increase in kidney C3 and C4 mRNA was observed; Factor B mRNA, which is expressed as a doublet in kidney and intestine, showed an increase in expression of the smaller transcript. This alteration of kidney C3, C4 and Factor B mRNA is identical to that noted in association with lupus nephritis in the MRL lpr/lpr strain and following in vivo administration of endotoxin to the BALB/c strain. The development of systemic lupus erythematosis (SLE) in the NZB/W F1 was not associated with a marked change in hepatic complement gene expression. These findings support the hypothesis that local production of complement may play a role in the pathogenesis of glomerulonephritis and other tissue injury in SLE.
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PMID:Complement gene expression in hepatic and extrahepatic tissues of NZB and NZB x W (F1) mouse strains. 222 28

In recent years defective function of the complement-mediated clearance of immune complexes (IC) has been reported in patients with immune complex disease. The defect has been found at different levels in the clearance system. An important event in this sequential system is the binding of C3-coated particles to C3 receptors on erythrocytes and phagocytes. This study focuses on immunochemical properties of IC-bound C3 that reflect the functional state of the molecule. Sera from patients with primary biliary cirrhosis (PBC), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and from normal subjects were analyzed for their level of C3 precipitable in 2.7% (w/v) polyethylene glycol (PEG). The mean levels for the patient categories were significantly higher than that for the normal subjects. The immunochemical study revealed several differences among the different forms of PEG-precipitable C3. All forms expressed C3(D) antigens which are expressed by immune complex-associated and denatured forms but not by soluble physiological forms of C3. The expression of these antigens was proportionately lower for the complex-associated C3 of PBC compared to that of RA and SLE. Furthermore, employing monoclonal anti-C3(D) antibodies against the C3c and the C3d domain, distinct differences could be detected among all forms of PEG-precipitable C3. Sera from RA and SLE, in particular, contained PEG-precipitable C3 that exhibited distinctive immunochemical features with respect to these epitopes.
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PMID:Quantitation and antigenic characterization of bound C3 of circulating immune complexes in systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis. 244 29


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