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)

We rescued from the spleens of 10 (SWR x NZB)F1 (SNF1) mice with lupus nephritis the T cells that were activated in vivo and cloned 268 T-cell lines and hybridomas. Only 12% of these T-cell clones had the functional ability to preferentially augment the production of pathogenic anti-DNA autoantibodies. Among these, 16 helper T-cell (Th-cell) clones that were mostly CD4+ and had the strongest autoantibody-inducing ability were analyzed for T-cell receptor (TCR) beta-chain gene usage. Seven of the 16 Th-cell clones expressed beta-chain variable region (V beta) V beta 8 (8.2 or 8.3) genes and three expressed V beta 4, whereas two clones each used a V beta 1 or V beta 2 or V beta 14 gene, suggesting some restriction in TCR gene usage. Although heterogeneous, the V-D-J junctional region sequences of TCR beta-chain genes used by these Th-cell clones invariably encoded one or more negatively charged residues (aspartic or glutamic acid) that had been generated in most cases by unspecified nucleotide (N) additions. Representative pathogenic autoantibody-inducing Th-cell clones could rapidly induce the development of lupus nephritis when injected into young prenephritic SNF1 mice. The pathogenic autoantibody-inducing Th cells expressing the anionic residues in their TCR beta-chain junctions (complementarity-determining region CDR3) were probably selected by some cationic autoantigenic peptide presented by the anti-DNA B cells they preferentially helped. These results offer a clue regarding the nature of the primary autoantigen that may drive the pathogenic autoimmune response in lupus.
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PMID:Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens. 183 46

We analysed the outcome of pregnancy in patients with pre-existing lupus nephritis, seen in a tertiary referral centre for nephrology. Fifty-three pregnancies in 25 patients who already had clinical and histological evidence of lupus nephritis were recorded between January 1970 and June 1989, and data were analysed retrospectively. All 53 pregnancies occurred in patients with more or less stable disease, while three pregnancies during which lupus first presented were excluded. Six pregnancies were ended by therapeutic abortions (four for social reasons), and in eight spontaneous abortion occurred. Thus, 39 deliveries occurred, 28 at 36 weeks or more, while 11 were delivered prematurely, of which one was a stillbirth. After allowance was made for therapeutic abortions, the fetal loss rate (9/47) was 19%. Seventeen Caesarian sections were performed in the 39 completed pregnancies (44%), 11 as emergencies. Although the overall fetal loss, incidence of premature births and Caesarian section rate were all higher than expected for a population of normal women, neither initial histology, treated hypertension, the presence of proteinuria or a nephrotic syndrome showed statistically significant relationships with the outcome of completed pregnancies. In no case was maternal renal function affected irreversibly, although proteinuria increased substantially during pregnancy in six patients, and creatinine clearance fell during pregnancy, also in six patients. No 'flares' in systemic disease were seen, but all patients save five were treated with a brief period of high-dose oral corticosteroids or intravenous methylprednisolone in the postpartum period. No case of neonatal lupus or congenital heart block was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1991 Nov
PMID:The outcome of pregnancy in women with lupus nephritis. 184 58

We review our experience with low-dose intravenous pulse cyclophosphamide as treatment of biopsy-proven lupus nephritis. Seventeen patients were treated with 2-4 (mostly 3) weekly low-dose intravenous pulses of cyclophosphamide (500 mg) and moderate doses of prednisolone (0.5 mg/kg/day), followed by an oral immunosuppressive drug (either azathioprine or cyclophosphamide). As compared with the classical monthly high-dose cyclophosphamide regimen, this weekly low-dose regimen induced neutropenia in one patient only. The incidence of herpes zoster was very low (6%). At the end of the follow-up period (15 +/- 8 months), two patients required chronic ambulatory peritoneal dialysis. The 14 patients that could be evaluated improved their mean serum albumin from 30 +/- 7 to 37.5 +/- 7 g/l (mean +/- SD; P < 0.01) and their mean serum creatinine fell from 125 +/- 119 to 101 +/- 66 mumol/l (not significant). Mean DNA binding dropped from 71 +/- 29 to 26 +/- 27% (P < 0.001) and mean complement fraction C4 levels increased from 14 +/- 8 to 28 +/- 18 mg/dl (P < 0.05). The mean daily prednisolone dose was dramatically reduced from 26 +/- 8 to 10 +/- 4 mg (P < 0.001). Although this preliminary and retrospective study clearly needs validation with a larger cohort followed for a longer period, it seems that a treatment combining moderate doses of steroids and 3-4 weekly low-dose intravenous pulses of cyclophosphamide, followed by oral immunosuppression, is well tolerated and beneficial--at least in the short term--for most patients with severe lupus nephritis.
Lupus 1991 Nov
PMID:Short course of weekly low-dose intravenous pulse cyclophosphamide in the treatment of lupus nephritis: a preliminary study. 184 61

To investigate the potential role of leukotrienes in murine lupus, we measured renal hemodynamics and renal leukotriene production in MRL-lpr/lpr mice at 12 and 20 weeks of age. Over this age range, these animals develop overt manifestations of autoimmune disease with nephritis similar to human SLE. In the current study, we demonstrated that glomerular filtration rate (GFR) and PAH clearance (CPAH) deteriorated with age in MRL-lpr/lpr mice, but not in MRL(-)+/+ controls. Impaired renal hemodynamic function in MRL-lpr/lpr mice was associated with enhanced ionophore-stimulated production of both leukotriene B4 (LTB4) and leukotriene C4 (LTC4) by preparations of renal cortex. There was a significant inverse correlation between GFR and in vitro production of both LTC4 and LTB4 in kidneys from MRL-lpr/lpr mice, but not in control animals. In addition, in vitro LTC4 production was correlated with the severity of renal histomorphologic abnormalities. Administration of the specific peptidoleukotriene receptor antagonist SKF104353 to 20 week old MRL-lpr/lpr mice significantly improved both GFR and CPAH, whereas this agent had no effect of renal hemodynamics in MRL(-)+/+ controls. These results suggest that renal production of LTC4 and LTB4 is increased in MRL-lpr/lpr mice with nephritis, and that enhanced production of peptidoleukotrienes causes reversible renal dysfunction. Increased leukotriene production within the kidney may therefore be important in the pathogenesis of lupus nephritis.
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PMID:Enhanced renal leukotriene production in murine lupus: role of lipoxygenase metabolites. 184 29

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). 186 81

Abnormal macrophages in MRL-lpr mice are implicated in the pathogenesis of autoimmune disease. These mice die of lupus nephritis by 5 to 6 months of age. This study reports that MRL-lpr mice have an increased level of circulating macrophage colony-stimulating factor (M-CSF) detectable as early as 1 week of age. Macrophage colony-stimulating factor decreased between 2 and 4 months and then steadily increased beginning at 4 months of age. In contrast, M-CSF was not detected in sera from congenic MRL-++ mice, normal C3H/FeJ mice, two other mouse strains with the lpr gene (B6-lpr and C3H-lpr), or another lupus model, the NZB/W mouse. These observations indicate that the lpr gene alone is not responsible for inducing this growth factor, and elevated M-CSF is not required for all forms of murine lupus. The entire source of serum M-CSF is not clear. The unique T cells regulated by the lpr gene are not responsible for the increased serum M-CSF levels, as no M-CSFs could be detected in supernatants from cultured lymph nodes from MRL-lpr mice, and the steady-state levels of M-CSF mRNA in lymph nodes and spleens in MRL-lpr, C3H-lpr mice and in their respective congenic strains were similar. The steady-state M-CSF mRNA transcripts in liver, lung, and bone marrow in MRL-lpr, MRL-++, and C3H/FeJ mice were also similar. Macrophage colony-stimulating factor transcripts were clearly elevated in the kidneys of MRL-lpr mice, suggesting a renal source of circulating M-CSF. The increase of M-CSF might be responsible for the increased numbers and enhanced functions of macrophages, which in turn cause tissue destruction in MRL-lpr mice.
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PMID:Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice. 186 17

We reviewed the initial serological data of 50 patients with biopsy-proven lupus nephritis. As compared with a group of lupus patients without nephritis, patients with nephritis had lower serum complement C3 (p less than 0.05) and C4 (p less than 0.005) levels and higher serum DNA binding activity (p less than 0.001). The frequency of rheumatoid factor, antiphospholipid, anti-ENA, and fluorescent antinuclear antibodies was similar in both groups. We correlated the serological data of the patients with nephritis with the clinical severity of their disease. Using a functional staging system based on the serum albumin and creatinine levels at the time of biopsy, we found that patients with functionally milder disease (proteinuria without nephrotic syndrome or renal failure) had higher C3 (p less than 0.05) and lower DNA binding (p less than 0.005) than patients in the more severe functional classes (nephrotic syndrome with or without renal failure). In contrast, C4 levels were always very low, irrespective of functional severity. We also correlated the serological data with the pathological findings. Patients suffering from diffuse proliferative nephritis had higher DNA binding values than patients with focal proliferative (p less than 0.01) or membranous (p less than 0.001) nephritis. By contrast, complement levels were not correlated with the severity of biopsy changes. Taken together, the data presented here suggest that C3 and DNA binding, but not C4, correlate with the clinical severity of lupus nephritis at presentation whereas DNA binding, but not complement levels, correlates with the severity of pathological changes.
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PMID:Lupus nephritis: the significance of serological tests at the time of biopsy. 193 81

Pregnancies complicated by collagen vascular diseases present a challenge to the obstetrician, internist, and other consulting physicians caring for the patient. Although most pregnancies complicated by these disorders result in satisfactory outcomes, a significant number develop manifestations sufficiently serious to require admission to an intensive care unit. Such manifestations include lupus nephritis, CNS lupus, ARDS, massive alveolar hemorrhage, scleroderma renal crisis, pulmonary hypertension, severe myositis, and diffuse vasculitis. Of the numerous therapeutic options available, many may be used to optimize maternal and perinatal outcome.
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PMID:Pregnancy complicated by collagen vascular disease. 194 52

As autoantibodies are thought to participate in the pathogenesis of renal inflammation in systemic lupus erythematosis (SLE) we investigated associations between serological markers of disease activity in SLE and the activity of renal histopathological lesions in thirty-five patients with lupus nephritis (LN). We found the following prevalence of serum auto-antibodies in LN: IgG antinuclear antibodies (ANA) 100%, IgM ANA 69%, IgA ANA 60%, IgG anti-dsDNA 60%, IgM anti-dsDNA 71%, IgA anti-dsDNA 60%, anti-RNP 20%, anti-Sm 14%, anti-SSA 31%, anti-SSB 14%, anti-histone 37%, anti-cardiolipin 80% and antibody to ribosomal protein (anti-P) 6%. No correlation was found between serological parameters and the WHO-classification of biopsies. The activity-index of histological lesion, assessed according to the NIH-renal histology scoring system, correlated with IgM ANA and IgM anti-dsDNA titers. Of all the specific features of histological renal inflammation, glomerular proliferation showed the best overall correlation with serological parameters of disease activity. Anticardiolipin antibodies were correlated with overall disease activity, but not with renal histological activity. Thus, serological markers of disease activity did not adequately reflect the amount of renal inflammation in LN and cannot replace renal biopsy as a diagnostic tool.
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PMID:Relation between serological data at the time of biopsy and renal histology in lupus nephritis. 194 73

Untreated 16-week-old MRL/MpJ-lpr/lpr (lpr) mice, when compared to congenic MRL/MpJ-+/+ (+/+) mice, are characterized by a systemic lupus erythematosus syndrome, including severe glomerulonephritis, proteinuria and reduction of renal function. We hypothesized that platelet activating factor (PAF), a potent chemotactic and proinflammatory phospholipid mediator synthesized and released by circulating cells, glomerular mesangial and renal medullary interstitial cells, may play a role in the development of renal injury in lupus mice. We assessed renal PAF synthesis in lpr as well as +/+ mice and the effect of treatment with a PAF receptor blocking agent. Treatment with the PAF receptor antagonist L659,989 for four weeks, starting at 12 weeks of age, significantly reduced acute glomerular infiltration and proliferation, and prevented chronic glomerular histological changes; proteinuria and serum creatinine levels were also significantly reduced in treated mice. Renal PAF production was increased in lpr when compared to +/+ mice, and treatment with L659,989 restored renal PAF synthesis to the control levels. Our results support the hypothesis that PAF can be one of the mediators of glomerular injury characteristic of murine lupus nephritis, and indicate the possible therapeutic utility of PAF receptor antagonists in immunologic renal diseases.
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PMID:Platelet activating factor receptor blockade ameliorates murine systemic lupus erythematosus. 196 46


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