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)

Specific double (D-DNA) and single stranded (S-DNA) deoxyribonucleic acid binding cells were demonstrated in the peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE) by rosette formation with antigen coated red blood cells. The proportion of DNA binding cells in the peripheral blood of patients with SLE was significantly higher than that found in a random population of healthy individuals. Significant numbers of D-and S-DNA binding lymphocytes were found in patients with active disease even when anti-DNA of fluorescent antinuclear antibodies disappeared. The specificity of the DNA binding cells was confirmed by inhibition experiments with D-or S-DNA. Spleen lymphocytes were also examined on one occasion and were found to contain a much higher level of DNA binding lymphocytes than the peripheral blood lymphocytes.
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PMID:Single and double stranded DNA binding lymphocytes in the peripheral blood of patients with systemic lupus erythematosus and normal controls. 31 37

Spleen cells from normal mice were cultured with Concanavalin A to produce an immunosuppressive supernate. This supernate was used to treat the lupus-like autoimmune disease of NZB/NZW mice. Such treated mice lived significantly longer than did controls, but only if treatment was initiated early in the course of the illness.
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PMID:Therapeutic studies in NZB/NZW mice. VI. Age-dependent effects of concanavalin A stimulated spleen cell supernate. 63 86

The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193-treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases.
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PMID:The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice. 163 62

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

The present study addresses the question of whether there is a difference in the frequencies of autoantibody-producing B-cell precursors in healthy compared with lupus-prone mouse strains. Spleen mononuclear cells (MNC) from 4-week-old (i.e. at the preclinical stage of lupus) mice were activated in vitro for 3 and 6 days with lipopolysaccharides (LPS) and the numbers of IgG, IgA and IgM autoantibody-producing cells were analysed by the ELISPOT assay. The results indicate a high frequency of IgM autoantibody-secreting cells after both 3 and 6 days in vitro stimulation. In spite of high frequencies of IgG-producing cells appearing late during the course of LPS stimulation, no IgG or IgA autoantibody producing cells were detected. No significant differences in the autoantibody repertoire were noted between healthy and lupus-prone mice, indicating that independent of the genetic background the immune system has the capacity to react with autoantibody production. Phenotypic analysis of LPS-induced, IgM-secreting B cells showed clearly that the majority of them were surface IgM+, CD5+ but Thy-1-.
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PMID:Frequency and phenotypic feature of autoantibody-producing cell precursors in the preclinical stage of murine lupus. 226 71

A patient with inactive systemic lupus erythematosus was successfully treated for pneumococcal sepsis complicated by disseminated intravascular coagulation, shock, renal failure, and functional asplenia. Functional asplenia was diagnosed from the total absence of uptake of intravenously administered 99mtechnetium-labeled sulfur colloid. Ten similar cases of functional asplenia occurring in patients with systemic lupus erythematosus were noted in a review of the literature. Six of these cases, including the current report, were complicated by pneumococcal (5) or salmonella (1) sepsis. The patient presented here had an excellent antibody response to pneumococcal vaccination. Spleen scan abnormalities fully reversed at 1 year. Although functional asplenia is a rare event in systemic lupus erythematosus, it appears to predispose to severe septic complications.
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PMID:Functional asplenia in systemic lupus erythematosus. 228 43

Previous reports have shown that Bacteroides fragilis may enhance the pathogenicity of coinfecting enterobacteriaceae by interfering with the host's immune response. With the present study, we have investigated the possible role of interferons (IFN) in mediating these effects. Mice injected with B. fragilis developed moderate serum levels of IFN that appeared just prior to alterations of the animals' immunity described earlier. The IFN was neutralized by treatment with anti-IFN-alpha/beta-antibodies or hydrochloric acid; hence it displayed the same "atypical" characteristics as IFN found in patients with immuno-compromising diseases such as AIDS, systemic lupus erythematosus or rheumatoid arthritis. Escherichia coli displayed the same induction patterns as B. fragilis, while gram-positive bacteria induced "regular" IFN alpha/beta and gamma. Spleen cells, peritoneal macrophages, or liver leukocytes taken from B. fragilis or E. coli-injected animals 6 h post infection were refractory to IFN induction by E. coli lipopolysaccharide in vitro; cells from mice infected with gram-positive organisms showed normal or enhanced responsiveness.
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PMID:Induction of an atypical interferon by bacteroides fragilis and Escherichia coli in experimental infections and in leukocyte cultures. 243 31

The production of antibodies to nucleic acids, and in particular to DNA, has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, little is known about the conditions under which DNA is immunogenic, particularly in well-characterized in vitro systems. Therefore, we examined whether a source of cytokines, in conjunction with D-DNA, permitted a polyclonal or antigen-specific B-cell response. Spleen cells from MRL +/+ SLE-prone mice were incubated with supernatant from concanavalin A-stimulated spleen cells (Con A SN, a source of cytokines) and D-DNA. A potent antibody response developed to guanosine (GU) and D-DNA but not to fluorescein (FL), using as little as 10 ng D-DNA in conjunction with Con A SN. In order to further examine the cellular requirements for D-DNA to be immunogenic, populations of B cells which bound GU (an immunodominant epitope of DNA) or an irrelevant FL-binding population were purified and incubated with DNA and Con A SN. Interestingly, GU-binding, but not FL-binding B cells could be triggered by D-DNA derived from calf thymus, a result suggesting that DNA was not acting simply as a polyclonal B-cell activator. D-DNA optimally triggered GU+ B cells within a narrow dose range similar to many thymus-independent Type II antigens with repetitive determinants. If DNA were truly an autoantigen, then DNA derived from the MRL +/+ mouse should be capable of triggering GU-binding B cells. When this hypothesis was tested, D-DNA, but not N-DNA, functioned as a potent immunogen. These experiments document the ability of DNA to act as a specific immunogen and suggest that, under appropriate conditions, nucleic acid may induce autoantibody production in vivo.
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PMID:DNA is a potent immunogen for spleen cells and for guanosine-binding B lymphocytes. 245 1

It was recently demonstrated that MRL-lpr lymphoid cells transferred into lethally irradiated MRL- +mice unexpectedly failed to induce the early onset of lupus syndrome and massive lymphadenopathy of the donor, instead they caused a severe wasting syndrome resembling graft-vs-host (GvH) disease. The present studies were carried out to characterize the cellular events involved in the severe GvH-like reaction developed in C57BL/6 (B6) recipients of B6-lpr spleen cells, designated as [B6-lpr----B6] chimeras. [B6-lpr----B6] chimeras showed at 2 weeks post transplantation marked splenomegaly consisting predominantly of Lyt2+ T cells (approximately 70%), and subsequently developed acute and severe depletion in spleen cells causing spleen atrophy and fibrosis. Spleen cells from chimeras at 2 weeks posttransfer were not cytotoxic to both recipient and donor ConA blast target cells. In contrast, those cells (irradiated to 3000 rad) considerably suppressed ConA-induced proliferative responses of B6 spleen cells. These nonspecific suppressor cells expressed Thy1 and Lyt2 antigens, but lacked L3T4 and B220 antigens. Furthermore, elimination of Thy1+ or B220+ but neither L3T4+ nor Lyt2+ cells from B6-lpr spleen cells before transfer retarded the generation of nonspecific suppressor cells but did not abrogate the GvH-like disease. These results suggest that the GvH-like disease and lymphoid atrophy in [B6-lpr----B6] chimeras were mediated by Lyt2+ suppressor T cells, and that B220+ T cells played a crucial role in the induction of these suppressor cells. The cell transfer model reported here may be very useful in understanding the immunological function of B220+ T cells in vivo.
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PMID:[Analysis of the mechanism of graft-vs-host like disease in [lpr/lpr----+/+] chimera]. 296 73

Mice which bear the lpr gene spontaneously develop autoimmune syndromes characterized by massive expansion of an unusual T cell subset which is phenotypically Thy-1+, L3T4-, Lyt-2-, B220+. The mutant T cells are refractory to stimulation with mitogenic lectins and, by implication, are thought to be solely responsible for the defects in lymphokine production manifested by lpr mice. The contribution of the remaining L3T4+ T cell subset to the latter derangements has not been previously examined and is the focus of this study. We found that abnormalities in concanavalin A-induced interleukin 2 and 3 production in the spleens of MRL-lpr/lpr and C57BL/6.lpr mice occurred in the presence of limited infiltration with B220+, L3T4- T cells. Mixing experiments indicated that B220+ T cells were not suppressive. Furthermore, lpr spleen cells enriched for L3T4+ cells and depleted of sIg+, B220+ and Lyt-2+ cells demonstrated reductions in lymphokine production which were comparable to those seen in unfractionated preparations. Spleen cells from C57BL/6.lpr mice, enriched for L3T4+ cells, were also markedly impaired in a mixed leukocyte reaction in response to stimulator cells from the class II major histocompatibility complex mutant bm12. The results indicate that the aberrations in lymphokine production and proliferation in the spleen cells of lpr mice involve not only B220+ T cells but also L3T4+ cells and suggest a potential role for the L3T4+ subset in the pathogenesis of lupus in lpr-bearing mice.
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PMID:The role of L3T4+ cells in the pathogenesis of lupus in lpr-bearing mice. I. Defects in the production of interleukins 2 and 3. 311 78


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