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)

Nucleosomes released spontaneously in short-term culture from murine spleen cells have a significant immunoproliferative effect in vitro, including the stimulation of anti-DNA antibody responses. The present studies show that during short-term cultures, tonsil lymphoid cells also undergo spontaneous apoptosis revealed morphologically (electron microscopy) by the appearance of changes in nuclear chromatin, typical of apoptosis and similar to morphologic changes of apoptosis in cultured normal splenic lymphocytes. This process is followed by the release, in the greater than 30-kDa cell free supernatant fraction, of core histones (H2A, H2B, H3, H4) and low molecular weight DNA (approx 160 bp) constituents of nucleosomes. The greater than 30-kDa tonsil lymphocyte cell-free supernatant material containing the constituents of core nucleosomes, as well as the greater than 30-kDa supernatant fractions of tonsil cell lysates harvested at the same time, had a significant immunoproliferative effect on human or murine lymphocytes, increasing both DNA and immunoglobulin synthesis (protein A plaque-forming cells). Thus the release of immunoproliferative nucleosomes form dying human lymphoid cells provides an autocrine lymphocyte stimulatory network which may be important in immunoproliferative disorders and in normal cell turnover. Apoptosis in vivo may also provide a potential source for the circulating nucleosomal DNA identified in plasma in some systemic lupus erythematosus patients as well as contributing to increased polyclonal B lymphocyte stimulation and autoantibody responses in this disorder.
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PMID:The spontaneous apoptotic cell death of normal human lymphocytes in vitro: the release of, and immunoproliferative response to, nucleosomes in vitro. 204 34

The influence of dietary fat on autoimmunity in lupus-prone (NZB x NZW)F1 mice has been demonstrated. In defining further the effects of dietary lipid on the immune system of this strain, female weanling mice were placed on four diets differing in quantity and type of fat. Their immunologic response was then studied by a variety of tests at 4 and 7 mo of age. Few differences were seen among the four groups at 4 mo of age. At 7 mo of age, however, the mice receiving diets high in saturated and unsaturated fats had a reduced mitogenic response to T cell mitogens and an enhanced response to the B cell mitogen LPS. Immunoglobulin levels and delayed hypersensitivity responses did not show any consistent differences among the diet groups. At 7 mo, however, mice receiving diets high in unsaturated fat demonstrated hyperresponsiveness to injected sheep red blood cells as measured by the hemolytic plaque technique. In addition, peritoneal leukocytes from the same diet group exhibited an increased response to bromelain-treated autologous erythrocytes which was decreased after treatment with anti-Thy-1 antiserum and complement. Phagocytosis by peritoneal macrophages was significantly decreased in the animals fed high-fat diets, particular high saturated fat. Similarly, natural killer cell activity was markedly reduced in the mice with a high intake of saturated lipid, a finding which correlated with the in vitro production of interferon. These results indicate that diets high in fat influence immune responses and thus can affect the onset and severity of autoimmune disease. A low-fat diet can reduce the development of disease by maintaining normal immune responses. The data also suggest that unsaturated fat may influence T helper cell activity and therefore antibody production, whereas saturated fats may affect cellular immune responses which are dependent on membrane contact.
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PMID:Dietary fat and immune function. I. Antibody responses, lymphocyte and accessory cell function in (NZB x NZW)F1 mice. 241 89

In murine models of systemic lupus erythematosus and in many humans with SLE, antibodies against native DNA (dsDNA) are a major contributor to the pathogenesis of the disease. Loss of self-tolerance to the DNA antigen may be associated with B-cell defects or regulatory cell dysfunction. We have developed B-cell lines with specificity for the antigen DNA, from both the autoimmune BWF1 mouse strain and from the non-autoimmune BALB/c strain, to use in the investigation of inherent B-cell defects in autoimmunity. Six BWF1 cell lines and five BALB/c cell lines which are free of Thy1.2+ cells and esterase positive cells, and have between 35 and 89% rosetting with dsDNA-SRBC targets, have been propagated in vitro for 24-36 months. The cells are non-malignant, growth-factor dependent and have no antigen or mitogen in the growth medium. Lyt-1 positive cells are found in the cell lines, but Lyt-1 negative cells are also present. They respond to the antigen DNA-HRBC when EL-4 supernatant is present in culture, and the peak of the plaque-forming cell (PFC) response is the same for both strains. When cells from both strains are cultured with varying amounts of T-cell factors, there is no difference in spontaneous antibody-forming cell (AFC) formation or in response to anti-mu stimulation between BWF1 and BALB/c strains. BALB/c spleen cells do not respond to DNA-HRBC in this culture system, but BWF1 spleen cells, as well as cell line cells from both strains, respond to this antigen. T cells from non-responding BALB/c spleen and responding BWF1 spleen are able to suppress the immune response to DNA-HRBC of cell line B cells from both strains. Propagating B-cell lines in the presence of DNA for 2 weeks stimulates BWF1 cell line cells, but suppresses the response of BALB/c cell lines to antigen.
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PMID:Investigations of intrinsic abnormalities in DNA-specific B lymphocytes from autoimmune mice. 252 8

A series of 72 women with polymorphic light eruption (PLE) seen between 1970-1988 was reviewed with regard to onset of the disorder and timing of oral contraceptive use and pregnancy. PLE is a light-induced dermatosis consisting of itching erythematous papular, plaque-like or eczematous skin lesions on exposed skin. It occurs mainly in women--79% in this series. Appropriate tests were performed to rule out systemic lupus erythematosus and porphyria. The mean age of onset was 25 years. 63.9% had used oral contraceptives during their disease. PLE and pill use was correlated in 15.3% of patients. No consistent relationship was found between PLE episodes and starting or stopping pills. Eruptions developed in 3 women during pregnancy; they worsened during pregnancy in 2; and resolved during pregnancy in 1 woman.
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PMID:Polymorphic light eruption induced by oral contraceptives and pregnancy? 273 45

In vitro culture of normal BALB/c spleen cells with staphylococcal enterotoxin B (SEB) activates antigen non-specific suppressor T cells (Ts) which can be assayed by their ability to suppress antibody production in a plaque assay. Addition of the experimental immunomodulatory drug Wy-18,251 (10-100 microM) to cultures of spleen cells plus SEB significantly increased Ts activity relative to cultures without the drug. Similar results were obtained with levamisole, but, in contrast, indomethacin (0.1-10 microM) inhibited SEB-induced suppressor cell activity. The ability of Wy-18,251 to augment Ts activity could be therapeutically useful in the treatment of those autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, in which hyperactive B cell function is a characteristic feature.
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PMID:Effects of Wy-18,251 (3-p-chlorophenyl)thiazolo[3,2-a]benzimidazole- 2-acetic acid), levamisole and indomethacin on the generation of murine T suppressor cells in vitro. 293 80

Lumin was administered at doses of 0.1 to 100 micrograms/kg for 5 months to NZB/W F1 mice as the model animal for studying systemic lupus erythematosus (SLE), a human autoimmune disease. The increase in anti-thymic autoantibody level was significantly inhibited at doses of 1 to 100 micrograms/kg. Also, the induction of suppressor T cells by concanavalin A was significantly promoted. In addition, recovery activity was significantly observed, over-coming the reduction in plaque-forming cell (PFC) response of anti-sheep erythrocytes at a dose of 100 micrograms/kg, as well as the reduction in PFC response of anti-trinitrophenylated-lipopolysaccharide at doses of 0.1 to 100 micrograms/kg. The above results prove that lumin exhibits an immunomodulating effect against immune disease in mice.
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PMID:[Immunopharmacological actions of lumin (II): Effect of lumin administration in NZB X NZW (B/W) F1 mice]. 295 70

Frozen kidney biopsy sections from nine patients with systemic lupus erythematosus (SLE) as well as many other renal diseases, including IgA nephropathy, membranous nephritis, and minimal change nephrotic syndrome, were negative for interferons -alpha and -gamma by immunofluorescence. Lupus patients studied included several subjects with marked serum elevations of interferon activity as well as others with low or negative serum interferon levels. Isolated glomerular eluates prepared from normal and SLE kidneys showed no functional interferon activity by virus plaque inhibition assay. Components of normal as well as SLE serum showed no direct binding to interferon -alpha or -gamma by ELISA assays.
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PMID:Absence of interferons-alpha and -gamma in renal lesions of systemic lupus erythematosus and membranous glomerulonephritis. 308 Dec 89

We have previously characterized the human B cell response to trinitrophenol (TNP)-Brucella abortus (Ba) response as being T cell independent. In this report we examine the role of monocytes in the TNP-Ba antibody response of human peripheral blood mononuclear cells (PBMC). Depletion of monocytes by sequential adherence to plastic and Sephadex G-10 passage did not result in decreased plaque-forming cell responses to TNP-Ba, suggesting that monocytes were not required. On the contrary monocytes were probably inhibitory because their removal resulted in enhanced responses. This was confirmed by showing that adding monocytes back reconstituted the inhibition. When interferon-gamma (IFN-gamma), a potent activator of monocytes, was added to TNP-Ba-driven PBMC cultures, marked inhibition (greater than 90%) of the responses ensued. This IFN-gamma-mediated suppression was monocyte dependent because it was completely abrogated by monocyte, but not T cell depletion. Previously, we described a concanavalin A (Con A), T cell inhibition pathway of the TNP-Ba response. Both the Con A and IFN-gamma pathways were tested for their ability to inhibit systemic lupus erythematosus (SLE) patient responses to TNP-Ba. The B cell response of SLE patients was inhibitable by both pathways. In all of the patients, the inhibition was complete (greater than 95%) when IFN-gamma was added to the cultures. In the presence of Con A, greater than 95% inhibition was observed in six of 10 patients, the remainder being inhibited to a lesser extent. Thus the hyperactive B cells from SLE patients can be down-regulated, particularly in the presence of IFN-gamma.
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PMID:The role of nonactivated and interferon-gamma activated monocytes in regulating normal and SLE patient B cell responses to TNP-Brucella abortus. 308 43

Palmerston North (PN) mice spontaneously develop autoimmune disease resembling SLE. Because immune responsiveness has not been defined in this strain, a study was designed to assay primary splenic plaque-forming cell (PFC) responses to thymus-dependent (TD) and thymus-independent (TI) Ag. Initial surveys of PN mice inoculated with the TD Ag SRBC showed adequate production of IgM PFC, but small numbers of IgG PFC were developed with polyspecific antiserum. In contrast, H-2-compatible DBA/1 control mice gave the expected responses to SRBC (IgG plaques elevated twofold compared with IgM plaques). PN mice had the usual responses to Ag that are largely TI; both PN and DBA/1 mice had active IgM and modest IgG responses to TNP-LPS and TNP-Ficoll. Additional experiments determined that PN mice had similar patterns of defective IgG responses to several different TD Ag (SRBC, horse RBC, and DNP-keyhole limpet hemocyanin). In each instance, the usual predominance of IgG1 plaques was absent, and total numbers of plaques developed with antisera specific for IgG isotypes were suppressed. Defective PN IgG production was evident as early as 3 wk of age, was not influenced by aging to 43 wk, and was not corrected by increasing the antigenic challenge 10-fold. PN spleen cells treated with monoclonal anti-Thy-1.2 and C were injected with pools of DBA/1 T cells into 850-rad irradiated (DBA/1 x PN)F1 hybrids. These recipients expressed low IgG1 responses to SRBC, suggesting that the B cell-containing fraction that was not lysed by anti-Thy-1.2 transferred the PN defect. PN mice, which do not respond to TD Ag with active IgG production, contradict the proposal that autoimmunity is associated with hyper-responsiveness to TD and TI Ag.
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PMID:Defective primary and secondary IgG responses to thymic-dependent antigens in autoimmune PN mice. 328 33

Peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) are hyporesponsive in vitro. In order to study the role of mononuclear phagocytes (m phag) in regulating the in vitro responses of autologous lymphocytes, the MNC from 16 SLE patients (eight active, eight inactive) and 14 healthy controls were stimulated in vitro with PHA or dsDNA. The proliferative response to PHA was tested by 3H-thymidine incorporation on day 4 and the response to dsDNA using a specific haemolytic plaque assay. Indomethacin, an inhibitor of prostaglandin (PG) synthesis by m phag, was added into the cultures to test the presence of suppressive m phag acting through a PG-mediated pathway. Indomethacin augmented the proliferative response to PHA in active SLE cultures and not in inactive SLE or controls. In six of 13 SLE cultures, dsDNA totally or partly suppressed anti-dsDNA plaque-forming cell (PFC) generation. Indomethacin restored or enhanced the PFC response to dsDNA in active SLE and not in inactive SLE or controls. M phag depletion by plastic adherence prevented the effects of indomethacin. These results show that m phage exerting a suppressive activity on PHA-induced lymphocyte proliferation and on anti-dsDNA antibody production are found in cultures from active SLE and generally not in inactive SLE or healthy individuals. PHA being primarily a T-cell stimulator, the m phag suppressive activity observed in PHA-stimulated cultures is exerted on T cells. On the other hand, in two active SLE cultures depleted of T cells by OKT3 antibody, indomethacin still could enhance the PFC response to dsDNA, showing that in vitro suppressive m phag can act directly on B cells from patients with active SLE.
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PMID:Mononuclear phagocytes from patients with active systemic lupus erythematosus down-regulate the specific in vitro reactivity of autologous lymphocytes to double-stranded DNA. 329 51


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