Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies (mAb) to lymphocyte function-associated antigen-1 (LFA-1) have been used successfully in vivo to inhibit immune responses and to block inflammatory reactions. To determine whether these effects of anti-LFA-1 could retard autoimmune disease, we treated lupus-prone NZB/NZW F1 (B/W) mice with a rat mAb to LFA-1 (anti-CD11a). Mice received high-dose therapy (500 micrograms twice weekly), low-dose therapy (40 micrograms thrice weekly), or phosphate-buffered saline from age 5 months to age 10 months. Treatment with high doses of anti-CD11a suppressed both the immune response to the rat mAb and the production of autoantibodies to double-stranded DNA. In contrast, treatment with low doses of anti-CD11a elicited an immune response to the rat mAb and did not suppress autoantibody production. The immunosuppressive effects of high doses of anti-CD11a were not due to target cell depletion. In fact, treatment induced a marked lymphocytosis which involved all lymphocyte subsets equally. Despite inhibiting autoantibody production, high-dose therapy had only modest effects on longevity.
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PMID:Treatment of murine lupus with monoclonal antibodies to lymphocyte function-associated antigen-1: dose-dependent inhibition of autoantibody production and blockade of the immune response to therapy. 805 Jan 93

To test the hypothesis that T-cells which exhibit abnormal immunological behavior manifest derangements in the de novo synthesis of phospholipids, the utilization of [3H]palmitic acid in B220+ T-cells from autoimmune MRL-lpr/lpr mice was investigated. The rate of incorporation of [3H]palmitic acid into membrane phospholipids was markedly increased in intact B220+ T-cells compared to that in T-cells from immunologically normal mice. The activities of two key enzymes involved in the de novo synthesis of palmitoyl-phospholipids, acyl-coenzyme (CoA) ligase and acyl-CoA; sn-glycerol-3-phosphate acyl transferase, were significantly higher in homogenates from B220+ T-cell membranes compared with those in controls. Despite these findings, the molar concentration of individual palmitoyl glycerolipids was equivalent in the membranes of B220+ T-cells and control lymph node T-cells. The results indicate that T-cells from lupus mice exhibit complex defects in the biosynthesis and turnover of membrane phospholipids and suggest the possibility that these aberrations contribute to T-cell dysfunction in autoimmune diseases.
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PMID:Long chain fatty acid utilization of T-cells from autoimmune MRL-lpr/lpr mice. 809 30

To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybrid (B/W) mice, and also to study the possible synergistic effect of both drugs, B/W mice were heminephrectomized at 32 weeks of age, and were divided into six groups. Each group of mice was treated with 50 microliters phosphate-buffered saline (PBS), 3 mg/kg methylprednisolone, 20 mg methylprednisolone, 0.6 mg DSP, 6 mg DSP, or with 3 mg methylprednisolone plus 0.6 mg DSP, s.c., four times per week for 8 weeks. Urine and blood samples (by tail vein venipuncture), as well as renal tissue specimens, were taken at 32 and 40 weeks of age. The degree of proteinuria, and serum anti-DNA activity (by ELISA) were determined. Renal specimens were evaluated with light- and immunofluorescence (C3)-microscopy, the degree of pathological changes being semi-quantitated and expressed as total light-microscopy (LM) and immunofluorescence (IF) scores. The survival rate at 40 weeks of age was significantly elevated in 0.6 mg DSP, 6 mg DSP, and methylprednisolone + DSP groups of mice compared with the control group. The appearance rate of significant post-treatment proteinuria was comparable among all groups. The difference (post-treatment titre--pretreatment titre) of serum anti-DNA activity in the 6 mg DSP and methylprednisolone + DSP groups were significantly less, while that of the 3 mg methylprednisolone group was greater compared with the control level. As for the total LM score, the levels significantly decreased in the 6 mg DSP, methylprednisolone + DSP and 3 mg methylprednisolone groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose 15-deoxyspergualin monotherapy surpasses methylprednisolone in its therapeutic effect on advanced lupus nephritis in New Zealand black/white F1 hybrid mice, and low-dose combination may be synergistic. 841 58

We report a woman with systemic lupus erythematosus (SLE) with diffuse proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical manifestations consistent with SLE without clinical evidence of scleroderma. The reactivity of her serum autoantibodies with the phosphoproteins ribosomal P, topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes comprised in part of phosphate groups. This may explain the unexpected coexistence of marker autoantibodies for SLE and scleroderma, possibly with implications for the mechanisms of autoantibody generation.
Lupus 1995 Aug
PMID:Autoantibodies to topoisomerase I in a patient with systemic lupus erythematosus without features of scleroderma. 852 30

Vitamin D has been discovered at the beginning of this century. 7-Dehydrocholesterol is converted to vitamin D3 in the skin and after several hydroxylations it is further converted to the active hormonal form, 1 alpha,25-(OH)2D3. Vitamin D stimulates the absorption of calcium and phosphate and is an essential link in bone resorption and formation and calcium metabolism. 1 alpha,25-(OH)2D3 acts through a vitamin D receptor. These receptors are not only present in clinical target organs (kidney, gut, liver) but can also be found in a wide variety of "non-classical" tissues (keratinocytes, cells belonging to the immune system). Moreover, numerous cells (keratinocytes, macrophages) can locally synthetize or can be induced to synthetize 1 alpha,25-(OH)2D3 and these cells are responsive to its action. When these data are combined, a possible paracrine function of 1 alpha,25-(OH)2D3 can be suspected. Via this paracrine function 1 alpha,25-(OH)2D3 can suppress the cellular and humoral immunity. Based on the discovery of these effects on immune cells in vitro it became clear that 1 alpha,25-(OH)2D3 might be an interesting molecule to prevent autoimmune diseases and organ transplantation. This has already been shown in several animal models (Heymann nephritis, diabetes mellitus, experimental allergic-encephalomyelitis, lupus). 1 alpha,25-(OH)2D3 demonstrates however some side-effects (hypercalciuria, hypercalcemia, bone resorption) and for this reason 1 alpha,25-(OH)2D3-analogs are developed with dissociated effects i.e. an activity profile that allows a specific action on non-classical tissues without calcemic effects. Some chemical modifications of the side chain, A and/or CD-ring results in "superanalogs" with 10 to 100-fold more activity on cell differentiation and the immune system then 1 alpha,25-(OH)2D3 but with less calcemic activity in vivo. These biological effects can be explained by differences in pharmacokinetics (low affinity for the plasma vitamin D-binding protein and short extracellular half-life) and increased intracellular activation and gen transactivation. Preclinical research must still be done to select the most potent superanalogs and to find the exact protocols for the prevention and treatment of autoimmune diseases and rejection of transplanted organs.
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PMID:[Immune modulation by vitamin D analogs in the prevention of autoimmune diseases]. 857 69

We describe a patient with subacute cutaneous lupus erythematosus, widespread pruritic papulosquamous plaques, and hypocomplementemia. Skin biopsy specimens revealed liquefaction degeneration and colloid bodies and dyskeratotic cells in basal and suprabasal layers. An immunofluorescence study revealed deposits of IgG, IgM, and C3 at the dermalepidermal junction in a bandlike pattern, and particulate IgG deposition in the basal and suprabasal layers. Treatment with prednisolone (15 mg/day), chloroquine phosphate (200 mg/ day), cyclosporine (5 mg/kg daily), and gold (10 mg/day) failed to reduce pruritic plaque formation, and pulse methylprednisolone therapy led to only a transient remission. Clinical exacerbations correlated with a decrease in complement levels. The disease was successfully controlled with dapsone (75 mg/day) and prednisolone (25 mg/day).
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PMID:Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy. 869 14

The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did not develop overt clinical signs of lupus and nephritis. The pathogenic T cell clones thus reside within the V beta 8.3+ T cell population, which includes an expanded T cell clone described previously. Finally, UDA alters the production of autoantibodies in a sex-dependent manner.
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PMID:Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice. 876 10

To understand the molecular mechanisms that are responsible for the B cell overactivity that is observed in patients with SLE, we have conducted experiments in which the surface immunoglobulin (sIg)-mediated early cell signaling events were studied. The anti-sIgM-mediated free intracytoplasmic calcium ([Ca2+]i) responses were significantly higher in SLE B cells compared with responses of normal individuals and to those of patients with other systemic autoimmune rheumatic diseases. The anti-IgD mAb induced [Ca2+]i responses were also higher in lupus B cells than in controls. The magnitude of anti-sIgM-mediated Ca2+ release from intracellular stores was also increased in B cells from SLE patients compared with normal controls. The amount of inositol phosphate metabolites produced upon crosslinking of sIgM was slightly higher in patients with lupus than in normal controls, although the difference was not statistically significant. In contrast, the degree of anti-sIgM-induced protein tyrosine phosphorylation was obviously increased in lupus patients. Our study demonstrates clearly for the first time that SLE B cells exhibit aberrant early signal transduction events, including augmented calcium responses after crosslinking of the B cell receptor and increased antigen-receptor-mediated phosphorylation of protein tyrosine residues. Because the above abnormalities did not correlate with disease activity or treatment status, we propose that they may have pathogenic significance.
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PMID:B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events. 895 17

Abnormal neurological functioning similar to that seen in systemic lupus erythematosus (SLE) patients is detectable in an SLE-prone murine strain (MRL/lpr) by 8-10 weeks and is severe by 18 weeks of age. The purpose of this study was to evaluate the effectiveness of murine antiintercellular adhesion molecule-1 (ICAM-1) in suppressing neurological disease in MRL/lpr mice. Beginning at 6 weeks of age, five MRL/lpr mice received 5 weekly intraperitoneal injections of anti-ICAM-1-containing culture supernatant in phosphate-buffered saline (PBS) whereas four animals were treated with non-anti-ICAM-1 containing supernatant in PBS. A decline in neurological functioning began in control mice by 10 weeks, but anti-ICAM-1 treated mice remained normal throughout the study. All control mice had vasculitic skin lesions by 14 weeks of age whereas none of the anti-ICAM-1 treated mice ever developed skin lesions. Nerve conduction studies performed on all mice prior to sacrifice showed sciatic compound motor action potentials of anti-ICAM-1 treated mice that were of higher amplitude and shorter latency than those of controls. Inflammation in the sciatic nerve was more common in control mice. Brain histology revealed a similar degree of choroid plexus inflammation in both groups. Our study demonstrated that anti-ICAM-1 was effective in suppressing neurological abnormalities in MRL/lpr mice and may potentially be useful therapy in human SLE.
Lupus 1997
PMID:Anti-intercellular adhesion molecule-1 (ICAM-1) antibody treatment prevents central and peripheral nervous system disease in autoimmune-prone mice. 936 23

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.
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PMID:Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. 973 Sep


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