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)

The formation of anti-DNA antibodies appears to be under a genetic control similar to that regulating the immune response to complex antigenic compounds. The ability to develop a high immune response to DNA seems to be predominantly dependent on the nature of the B-cell population whereas a major role of the T-cell suppressor population is not evident in this response. The immune response to DNA does not necessarily need the presence of thymus-derived lymphocytes, but in some cases T-cells may exert a helper effect. The development of anti-DNA antibody response may be triggered by various factors: viral, bacterial or parasitic agents, tissue destruction or some drugs. A mechanism that may play an important role is the "nonspecific" triggering of anti-DNA antibodies by substances that, like bacterial lipopolysaccharides, exert a potent stimulatory effect on B-cells and simultaneously induce a release of DNA in extracellular fluids. In lupus diseases as well as in mice injected with lipopolysaccharide, pathogenic effects of anti-DNA antibodies appear to be closely related to the formation of DNA-anti-DNA complexes. The demonstration that injections of lipopolysaccharide lead to the localization of DNA-anti-DNA complexes in kidney glomeruli stressed the possible importance of stimuli responsible for a release of DNA in circulating blood in the expression of the pathogenic effects of anti-DNA antibodies.
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PMID:Genesis and pathogenicity of anti-DNA antibodies. 13 82

It is widely believed that autoimmunity is an integral part of the immune system, and that genetic, immunologic, hormonal, environmental and other factors contribute to the pathogenesis of autoimmune disease. Thus, autoimmune disease may represent an abnormal expression of immune functions instead of loss of tolerance to self, and it can be organ specific or systemic in its manifestations. We review the various factors that contribute to the development of autoimmune disease; we also review the mechanisms of polyclonal B-cell activation, with emphasis on the role of infectious agents. We consider systemic lupus erythematosus in humans and in experimental animals as prototypic autoimmune disease, and we summarize data to indicate that polyclonal B-cell activation is central to the pathogenesis of systemic autoimmune disease. The effect of polyclonal B-cell activation, brought about by injections of a B-cell activator-lipopolysaccharide from Gram-negative bacteria-is sufficient to cause autoimmune disease in an immunologically normal host. In fact, autoimmune disease can be arrested if excessive polyclonal B-cell activation is suppressed; alternatively, autoimmune disease can be exacerbated if polyclonal B-cell activation is enhanced. We explore the mechanism of tissue injury when autoimmune disease is induced or exacerbated, and we consider the pathogenic roles of autoantibodies, immune complexes, complement, the blood cell carrier system, and the mononuclear phagocyte system. Although polyclonal B-cell activation may be the mechanism whereby various factors can cause or exacerbate systemic autoimmune disease, polyclonal B-cell activation may cause autoimmune disease on its own.
Lupus 1992 Feb
PMID:Autoimmunity, polyclonal B-cell activation and infection. 130 66

We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice.
Lupus 1992 Aug
PMID:Bacterial lipopolysaccharide causes variable deposits of diverse immunoglobulin isotypes in kidneys of lupus-prone mice. 130 89

Human TNF alpha locus locates between HLA-B and DR region on the short arm of chromosome 6. The 5.5 kb and 10.5 kb of TNF alpha restriction fragment length polymorphic (RFLP) bands were identified by Southern hybridization using a restriction enzyme, NcoI. The frequencies of those bands were not different among patients with systemic lupus erythematosus (SLE), those with rheumatoid arthritis and normal controls. In the lupus patients, proteinuria was more frequent in the patients with the 5.5 kb RFLP band (19/39: 48.7%) than those without 5.5 kb band (7/35: 20%) (p less than 0.05). Furthermore, this band was strongly associated with the haplotype HLA B44-DRw13-DQw1. In order to investigate the association between this gene polymorphism and the production of TNF alpha, peripheral blood mononuclear cells from patients with SLE and normal controls were cultured for 24 hours with lipopolysaccharide and concanavalin A and the amount of TNF alpha in the supernatant was measured by enzyme linked immunosorbent assay. The TNF alpha production of lupus patients was not statistically different from that of normal controls. The production of TNF alpha was not related to 5.5 kb RFLP band, but in the patients with SLE, the mean value of TNF alpha in patients with the 5.5 kb RFLP band tended to be higher than those without the band. Lupus patients were divided into two groups by the production of TNF alpha i.e. low TNF alpha inducibility group and high TNF alpha inducibility group. Patients with proteinuria were more frequent in patients of the high TNF alpha inducibility group than those of low TNF alpha inducibility group (p less than 0.05). There were four patients with HLA B44-DRw13-DQw1 who had the 5.5 kb RFLP band and three of them belonged to the high TNF alpha inducibility group with nephrosis. These data suggest that TNF alpha and HLA are possibly associated with the severity of lupus nephritis.
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PMID:[Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by restriction fragment length polymorphism and production by peripheral blood mononuclear cells]. 135 65

The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.
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PMID:Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro. 137 63

Inhibition experiments were performed to study the specificity of IgG-class antibody, binding to cardiolipin immobilized onto a polystyrene surface, in sera from patients with systemic lupus erythematosus (SLE) or infection. Six different phospholipids (three anionic: cardiolipin, phosphatidylserine and phosphatidic acid, and three neutral: phosphatidylcholine, phosphatidylethanolamine and platelet activating factor), lipopolysaccharide from Salmonella Minnesota (ReLPS), strain Re595 and lipoteichoic acid from Streptococcus pyogenes were used as inhibitors, in the form of liposomes. Eight of fifteen SLE sera exhibited strong reactivity to phosphatidylserine liposomes; other anionic phospholipids, cardiolipin and phosphatidic acid, were less effective inhibitors. The binding was inhibited effectively only by cardiolipin in three of the SLE sera, and by none of the anionic phospholipids tested in the remaining four SLE sera. In most sera from patients with bacterial infections (including syphilis), anti-cardiolipin antibodies (ACA) were inhibited only by cardiolipin, but in some cases also by phosphatidic acid. In Gram-negative infections, ACA were inhibited by ReLPS more effectively than by cardiolipin. ReLPS also inhibited ACA in two of five chlamydial sera. Appreciable inhibition of ACA by phosphatidylserine did not occur in infections. Thus, in contrast to previous studies, broad reactivity to anionic phospholipids occurred in only about half of SLE sera. This pattern of polyreactivity was not seen in infections.
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PMID:Binding profiles of anticardiolipin antibodies in sera from patients with SLE and infectious diseases. 179 29

Systemic autoimmune disease is influenced by genetic, immunological, hormonal, and environmental factors. Although environmental factors are major agents that induce or exacerbate autoimmune diseases, the mechanism(s) and the molecular events by which they operate remain poorly understood. Here we used the lupus-prone BXSB mouse as an animal model of systemic autoimmune disease, and we used a bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism(s) by which infectious agents exacerbate autoimmune diseases. Our experimental protocol was designed to address three questions: (i) whether spontaneous polyclonal B cell activation (PBA) that occurs in BXSB mice could be further enhanced by bacterial LPS; (ii) whether repeated exposure to LPS would exacerbate autoimmune disease, as reflected by enhanced deposits of immune complexes (ICs) in kidneys and exacerbated nephritis; and (iii) whether the mechanism by which LPS exacerbates nephritis might involve interference with blood cell carrier function, mononuclear phagocyte function, or both. BXSB mice were injected with LPS (25 micrograms) twice a week for 5 weeks; control autoimmune BXSB mice and immunologically normal (C57BL/6) mice were injected with vehicle only. The three groups of mice were then challenged with soluble ICs to assess the kinetics of their disappearance from the circulation, their uptake by the mononuclear phagocyte system (liver, spleen), their distribution in target organ (kidney), and blood cell carrier function. The results indicate that: (i) spontaneous PBA can be enhanced further by LPS; (ii) exposure to LPS results in increased deposits of endogenous ICs in kidneys and exacerbated nephritis; and (iii) defective handling of ICs by the mononuclear phagocyte system and impaired blood cell carrier function are contributory factors to exacerbated nephritis, but that mechanisms in addition to passive localization of ICs may also be operative.
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PMID:Bacterial lipopolysaccharide enhances deposition of immune complexes and exacerbates nephritis in BXSB lupus-prone mice. 186 8

We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE.
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PMID:Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE). 189 18

The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.
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PMID:Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice. 191 23

Fluorescent light emitted from cool white tubular fluorescent lamps covered with standard acrylic lids decreased autoimmunity and enhanced immunity in the New Zealand Black/New Zealand White F1 hybrid female (B/W) mouse model of systemic lupus erythematosus (SLE). Thirty-three weeks of daily cool white fluorescent light exposure significantly decreased anti-ds DNA antibody levels and spleen size, and increased lymphocyte responsiveness to lipopolysaccharide (LPS) in B/W mice depilated to enhance light penetration. Depilation alone had no significant effect. The immunomodulatory potential of fluorescent light in B/W mice has not been previously appreciated, and may have important implications in SLE.
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PMID:Fluorescent light decreases autoimmunity and improves immunity in B/W mice. 196 47


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