Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We describe the case of a 25-year-old woman who developed soft tissue ectopic nephritis. Ectopic calcinosis rarely occurs in systemic lupus erythematosus (SLE) patients. This is the first detailed case report of metastatic ectopic calcinosis, one of two categories of ectopic calcinosis, probably due to 1 alpha-OH-vitamin D3 therapy. We administered disodium 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate pentahydrate, a second-generation bisphosphonate, to decrease the patient's serum calcium level, and subsequently observed a dramatic decrease in severity of the ectopic calcinosis along with decreases in both the serum calcium level and the (serum calcium level)x(serum phosphate level) index. We suggest that 1 alpha-OH vitamin D3 should be used in cases of lupus nephritis with great caution.
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PMID:Periarticular ectopic calcinosis probably due to 1 alpha-OH-vitamin D3 therapy, and successful treatment with bisphosphonate compound in a patient with systemic lupus erythematosus. 912 69

The present study was made to investigate the effect of mizoribine (MZR), an imidazole nucleoside immunosuppressant, on pulmonary lesions and immunological mode of action of MRL/lpr/lpr mice. Four-week-old female MRL/lpr/lpr mice were injected subcutaneously with 20 mg/kg body weight of MZR every other day. For control, mice were given phosphate-buffered saline (PBS) every other day. MZR caused the delay in the histological development of peribronchial and perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr (MRL/lpr) mice. And then, MZR suppressed the number of immunoglobulin (Ig) (IgG and IgM) secreting B cells and anti-DNA-secreting B cells in the spleen of MRL/lpr/lpr mice. The above data indicate that MZR could be useful for the treatment of pulmonary lesions associated with autoimmune disorders such as systemic lupus erythematosus (SLE).
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PMID:Effect of mizoribine on pulmonary lesions in MRL/lpr/lpr mice. 916 96

The recognition of DNA-like phosphorylated polymers by anti-DNA antibodies from the plasma of systemic lupus erythematosus patients was evidenced a few years ago by our research group. However, the radioimmunological Farr assay used for the assessment of anti-DNA antibodies adsorption was not sensitive enough to give accurate results, particularly in the case of weak levels of antibodies. An alternative method based on the use of radiolabelled species was set up in order to check the validity of previous results. Polystyrene resins with different levels in phosphate groups substitution were assessed with regard to their interactions with anti-DNA antibodies. Results show that the anti-DNA antibodies affinity is dependent on the composition of the polymers and reaches a maximum for a composition of 17.5-22.5 mol of phosphorus per 100 mol of monomeric units. This composition corresponds to the DNA-like polymer previously described. A computer-assisted method was used in order to have an insight into the structure of the active sites responsible for the DNA-like behaviour of this polymer. Numerical simulations of the phosphorylation reaction were performed using a Monte Carlo method, taking the structure predictions and the environment of the phosphorylated units into account. A number of thus generated virtual polymers correlated with the experimental results of the adsorption of anti-DNA antibodies. The chemical structure of the active site was determined by computations introducing selected hypotheses on the structure of the phosphorylated units. Moreover, since the number of active sites is directly related to the number of adsorbed anti-DNA antibodies in the experimental results, the most probable structure of the active sites is proposed and compared to a fragment of DNA. Conclusions are that the distances between the phosphate groups in the active sites of the DNA-like polymer and in the DNA fragment are similar. Optimal conditions for the purification of SLE sera by highly specific liquid chromatography using phosphorylated polystyrene resins of precise compositions as stationary phases can thus be envisaged, as well as a new method for the detection of anti-DNA antibodies.
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PMID:Biospecific polymers: recognition of phosphorylated polystyrene derivatives by anti-DNA antibodies. 919 32

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

The objective of this study was to assess the impact of murine recombinant IFN-gamma and anti-IFN-gamma monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16/6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-gamma, anti-IFN-gamma mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-gamma, intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-gamma treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-gamma treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-gamma treated mice. IFN-gamma upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-gamma administration can aggravate the clinical and laboratory outcome of 16/6 id induced lupus in BALB/c mice.
Lupus 1998
PMID:Immunomodulation of murine experimental SLE-like disease by interferon-gamma. 979 46

A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes.
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PMID:Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. 1035 96

Phosphorylation of complement component C3 by different protein kinases in vitro has been demonstrated to alter the functional properties of the protein. Extracellular phosphorylation mediated by activated platelets is a newly described mechanism by which the function of plasma proteins can be regulated. Upon activation of platelets a casein kinase is released concomitant with large amounts of ATP and Ca2+. These components are sufficient to phosphorylate proteins e.g., C3 extracellularly. In vivo, in patients with SLE, the phosphate content in plasma proteins, including C3 has been demonstrated to increase during exacerbation. The changes were linked to platelet activation by a covariation with the levels of beta-thromboglobulin. The purpose of this review is to summarise the findings in this field.
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PMID:Phosphorylation of plasma proteins with emphasis on complement component C3. 1040 76


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