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)

In a 10-year retrospective study, we evaluated the clinicopathologic features and renal immunofluorescence patterns of glomerulonephritis in 41 dogs. On the basis of results of histologic examinations, the dogs were segregated into 3 groups, including membranous (n = 12), mesangioproliferative (n = 15), or membranoproliferative glomerulonephritis (n = 14). No significant differences existed among groups in regard to age or duration of illness. Most dogs had been ill for one month or longer. The proportion of dogs with azotemia, anemia, and hyperphosphatemia were not different among the disease groups. Proportion of dogs with hypoalbuminemia and the severity of hypoalbuminemia were not different among groups. Highest urine protein losses and 24-hour urine protein/creatinine ratios developed in dogs with membranous glomerulonephritis. Although hypoalbuminemia and hypercholesterolemia were common (49%), the formation of edema or ascites was not (15%) and, therefore, few dogs had all of the classic features of the nephrotic syndrome. Few dogs suffered thromboembolic complications. Antinuclear antibody titers developed in 11 dogs, the highest titers developing in dogs with polyarthritis and systemic lupus erythematosis. Cellulose acetate electrophoresis detected alpha 2 and beta 1 globulin spikes in most dogs (87%). Results of renal immunofluorescence testing were positive in 36 dogs, using polyvalent antisera for immunoglobulins (Ig)G, IgA, IgM, and/or antisera for complement factor C3. When monovalent antisera for IgG, IgA, and IgM, and fibrinogen were used, immunofluorescence was not observed as often. The major fluorescent pattern was discrete multifocal segmental granular glomerular fluorescence, consistent with immune-complex deposition. Two dogs had linear glomerular staining patterns; however, antibodies directed against normal glomerular basement membrane were not found via elution studies. A high prevalence of glucocorticoid excess (treatment with glucocorticoids and spontaneous hyperadrenocorticism) (34%), chronic inflammatory skin disease (27%), neoplasia (17%), polyarthritis (12%), and systemic lupus erythematosis (7%) were observed as clinical problems concurrent with glomerulonephritis. In 5 dogs, treatment of glomerulonephritis with prednisolone (0.5 to 1.1 mg/kg) did not result in beneficial effects and in fact appeared to be detrimental, leading to azotemia and worsening proteinuria and physical condition in some of the dogs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985). 354 34

Several adhesion molecules and CD45RO have been reported to be upregulated on the cell surface of 'memory' T cells. Using triple-color flow cytometry, we compared the levels of typical 'memory' cell markers on peripheral blood T-cell subpopulations in a number of kidney transplant recipients, patients with systemic lupus erythematosus, newborn infants and healthy donors. CD45RO, VLA-beta 1 (CD29), VLA-5 alpha (CD49e), LFA-1 (CD11a/18), and CD2 were found to be closely coregulated on CD4+ T cells, while regulation of VLA-2 alpha (Cd49b), VLA-4 alpha (CD49d) and CD44 was quite discordant. In CD8+ T cells, by contrast, multiple subsets of 'memory'-type cells were distinguished. Unlike TCR alpha/beta T cells, which expressed either high or low levels of LFA-1, TCR gamma/delta cells all expressed high levels of LFA-1 (CD11a/CD18). Examination of T cells from kidney graft fine-needle aspiration biopsies during rejection revealed intragraft accumulation of 'memory'-type T cells expressing high levels of CD2 and LFA-1 (CD11a/CD18). Regarding peripheral blood T-cell subsets, differences between patients and healthy controls were only of a quantitative nature.
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PMID:Discordant expression of LFA-1, VLA-4alpha, VLA-beta 1, CD45RO and CD28 on T-cell subsets: evidence for multiple subsets of 'memory' T cells. 752 37

MRL lpr/lpr mice suffer from a systemic lupus erythematosus-like autoimmune disease. The lpr mutation impairs the normal transcription of the fas message, the product of which mediates apoptosis and presumably the proper selection of T cells. We have found an early expansion of CD4+ T cells bearing a distinctive V beta 8.3-D beta 1.1-J beta 1.1 T cell receptor beta chain in the periphery of MRL lpr/lpr mice, which was not detected in MRL +/+ mice nor in the thymus of MRL lpr/lpr mice. Thus, since thymic selection is normal in MRL lpr/lpr mice, we propose that the lpr mutation results in defective negative selection at the periphery.
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PMID:The expansion of a CD4+ T cell population bearing a distinctive beta chain in MRL lpr/lpr mice suggests a role for the fas protein in peripheral T cell selection. 752 3

The present study was carried out to determine whether restricting dietary calories prevents salivary gland abnormalities and modulates expression of transforming growth factor beta and proinflammatory cytokines, IL-6, and TNF alpha in major salivary glands (SG) of autoimmune lupus-prone (NZB x NZW)F1 (B/W) female mice. These mice develop focal lymphocytic interstitial and periductal round cell infiltrates in salivary glands similar to those of humans with Sjogren's syndrome. Weanling B/W mice were fed a nutritionally adequate semipurified diet either ad libitum (AL) or a calorie-restricted (CR; 40% less calories than AL) diet. The mice were sacrificed at 3.5 months (young) and 8.5 months (old) of age. Histopathologic and histomorphometric analyses as well as growth factor and cytokine protein and mRNA expression were carried out in the SG. Histomorphometric analysis of SG from young mice showed no differences between AL and CR mice, but old AL (vs old CR) had a 7.3-fold higher focus score and a 34-fold increase in percentage area inflammation. mRNA analysis revealed significantly higher levels of TGF beta 1 in SG of old CR (6.8-fold) mice. In contrast, CR reduced mRNA expression of proinflammatory cytokines (IL-6, 2.9-fold for young and 4.8-fold for old; TNF alpha, old 3.9-fold). By immunoblotting, significantly higher levels of TGF beta 1 protein was detected in old CR mice (vs old AL; 13.2-fold). IL-6 and TNF alpha proteins were undetectable in both young and old CR groups, whereas an increase in IL-6 (4.7-fold) and TNF alpha (9.3-fold) was observed in old AL mice. These results indicate that amelioration of the histological severity of disease in SG of B/W mice is paralleled and possibly mediated by increased expression of immunosuppressive TGF beta 1 and decreased expression of proinflammatory cytokines.
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PMID:Effects of calorie restriction on transforming growth factor beta 1 and proinflammatory cytokines in murine Sjogren's syndrome. 755 51

The present study was carried out to test whether transforming growth factor beta (TGF beta) plays a pathological role in the induction or progression of glomerulonephritis in a murine model of systemic lupus erythematosus (SLE), and whether dietary supplementation with fish oil (FO) can modulate the expression of TGF beta. Weanling female (NZB x NZW) F1 (B/W) mice were divided into three groups. One group was fed an unmanipulated diet (lab. chow; LC) and the other two groups were fed a nutritionally adequate semipurified diet supplemented with 10% CO or FO. Both water and food were provided ad libitum. Proteinuria and serum anti-dsDNA antibody levels were measured to assess disease progression. Mice were killed at 3.5 and 6.5 months of age and renal mRNA levels for TGF beta isoforms, fibronectin-1 (FN-1) and intercellular adhesion molecule-1 (ICAM-1) were studied by Northern blot analysis. TGF beta 1 protein levels were also examined in kidneys by Western blot analysis. Our results indicate that at 3.5 months of age, when urinary protein levels were undetectable and very low levels of anti-dsDNA were detected, no mRNA signal could be detected for TGF beta isoforms, ICAM-1 and FN-1 in either dietary group. However, at 6.5 months, the FO-fed mice, compared to LC and CO, had [1] greatly reduced proteinuria (LC: 2-3+, CO: 2-3+; FO: trace -1+) and serum anti-dsDNA antibodies; [2] improved survival (CO: 100% death (15/15) occurred by 8 months; FO: 50% were alive at 12 months (8/15) and [3] reduced renal TGF beta 1 mRNA and protein levels. TGF beta 2 and beta 3 were not significantly affected by FO diet. Similarly, lower levels of renal FN-1 and ICAM-1 mRNA were observed in FO fed mice. These data indicate that in B/W mice on a FO diet, prolonged survival and amelioration of renal disease may be attributed at least in part to lower levels of TGF beta 1 mRNA and protein in the kidneys.
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PMID:Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. 757 99

The nature of the stimuli driving autoantibody production in systemic lupus erythematosus (SLE) is unclear, but cytokines are believed to play an important role. Since cytokines primarily appear to act locally at the tissue level, we analysed mRNA expression of several cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN gamma, TNF alpha, TNF beta and TGF beta 1) in the lymph nodes of lupus-prone mice, in models of early onset disease. We constructed a multispecific competitor fragment that allowed quantification of these cytokine transcripts by competitive PCR assay. The results reveal considerable overexpression of IL-1 beta, IL-10 and IFN gamma transcripts in SLE-prone MRL-lpr/lpr (MRL/l) and BXSB male (BXSBm) mice, but with some strain differences. IFN gamma was most markedly augmented in MRL/l mice (in some cases over 100-fold greater than control mice), IL-1 beta was most severely overexpressed in BXSBm mice while IL-10 was equally increased in both strains. In addition, TGF beta 1 expression was moderately elevated in the lymph nodes of BXSBm (but not MRL/l) mice. We found no abnormality in the expression of the other cytokines. Cytokine transcript levels were only slightly altered at 4 weeks of age, but were elevated from 10 to 22 weeks of age. The latter phase corresponds to a period where lupus-like disease escalates, resulting in frequent mortality. Interestingly, our results do not reveal a clear Th1 or Th2 cytokine expression pattern in these lupus-prone mice. IL-1 beta, IFN gamma and IL-10 are pleiotropic cytokines with pro-inflammatory and B-cell stimulatory effects. These results point to certain cytokines as potential targets for immunotherapy in lupus.
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PMID:Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice. 778 52

T cells that recognize autoantigens may play a central role in the autoimmune response. We have previously shown that autoantigen-reactive T cells (CD4+) to U1-small nuclear ribonucleoprotein A were found in the PBMC of patients with systemic lupus erythematosus or mixed connective tissue disease. To reveal clonotypes of such T cells that spread to the periphery, T cell clonal accumulations and their TCR-beta chain variable gene usages in fresh PBMC from eight patients with mixed connective tissue disease were analyzed by a new method of single strand conformation polymorphism applying to TCR gene detection. The results revealed that the numbers of accumulated T cell clones (mean: 24.3 clones) were greater than the numbers of clones detected in healthy donors (mean: 4.0 clones). Frequently used V beta genes in these accumulated T cell clones were V beta 1, 3, 4, 5.2, 14, and 16. After the stimulation for these samples with the soluble recombinant U1-small nuclear ribonucleoprotein A protein, proliferative T cell responses were observed. We found that T cell clones expressing more restricted TCR V beta genes (1, 3, 5.2, and 14 families) accumulated in vitro. These results suggest that autoantigen-reactive oligoclonal T cell accumulations are present in the peripheral blood from systemic autoimmune disease patients.
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PMID:Clonotype analysis of peripheral blood T cells and autoantigen-reactive T cells from patients with mixed connective tissue disease. 793 May 95

Infection with gram-negative and gram-positive bacteria remains a leading cause of death in patients with systemic lupus erythematosis (SLE), even in the absence of immunosuppressive therapy. To elucidate the mechanisms that underly the increased risk of infection observed in patients with systemic autoimmunity, we have investigated host defense against bacterial infection in a murine model of autoimmunity, the MRL/Mp-lpr/lpr (MRL/lpr) mouse. Our previous study implicated transforming growth factor beta (TGF-beta) in a novel acquired defect in neutrophil function in MRL/lpr but not congenic MRL/Mp-+/+ (MRL/n) mice (Gresham, H.D., C.J. Ray, and F.K. O'Sullivan. 1991. J. Immunol. 146:3911). We hypothesized from these observations that MRL/lpr mice would have defects in host defense against bacterial infection and that they would have constitutively higher local and systemic levels of active TGF-beta which would be responsible, at least in part, for the defect in host defense. We show in this paper that spontaneous elaboration of active TGF-beta adversely affects host defense against both gram-negative and gram-positive bacterial infection in MRL/lpr mice. Our data indicate that MRL/lpr mice, as compared with congenic MRL/n mice, exhibit decreased survival in response to bacterial infection, that polymorphonuclear leukocytes (PMN) from MRl/lpr mice fail to migrate to the site of infection during the initial stages of infection, that MRL/lpr mice have a significantly increased bacterial burden at the site of infection and at other tissue sites, and that this increased bacterial growth occurs at a time (> 20 h after infection) when PMN influx is greatly enhanced in MRL/lpr mice. Most intriguingly, the alteration in PMN extravasation during the initial stages of infection and failure to restrict bacterial growth in vivo could be duplicated in MRL/n mice with a parenteral injection of active TGF-beta 1 at the time of bacterial challenge. Moreover, these alterations in host defense, including survival in response to lethal infection, could be ameliorated in MRL/lpr mice by the parenteral administration of a monoclonal antibody that neutralizes the activity of TGF-beta. These data indicate that elaboration of TGF-beta as a result of autoimmune phenomenon suppresses host defense against bacterial infection and that such a mechanism could be responsible for the increased risk of bacterial infection observed in patients with autoimmune diseases.
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PMID:Spontaneous elaboration of transforming growth factor beta suppresses host defense against bacterial infection in autoimmune MRL/lpr mice. 796 55

The urinary transforming growth factor beta (TGF-beta) excretion was measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN), and 6 with membranous nephropathy (MN), and in 7 healthy subjects by enzyme-linked immunosorbent assay using a monoclonal antibody specific for TGF-beta 1 + 2 + 3. A significantly increased urinary TGF-beta excretion was observed in FGS patients (555.5 +/- 458.4 ng/mg Cr) as compared with normal controls (46.9 +/- 43.9 ng/mg Cr) (p < 0.05) and a relative increase in SLE patients (96.4 +/- 58.2 ng/mg Cr) and a decrease in MN patients (24.8 +/- 13.3 ng/mg Cr). In contrast, there was no difference in TGF-beta excretion between IgAN patients (54.1 +/- 37.4 ng/mg Cr) and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found. As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. The results obtained in this study raised the possibility that extracellular matrix might be produced by glomerular cells in vivo under the control of TGF-beta and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.
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PMID:Increased excretion of urinary transforming growth factor beta in patients with focal glomerular sclerosis. 801 40

Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.
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PMID:Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin. 833 95


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