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)

The role of genetic factors in controlling CR1 quantitative expression on erythrocytes (E) of patients with systemic lupus erythematosus (SLE) was reexamined by determining the temporal stability of CR1 numbers and the frequency of a CR1 genomic restriction fragment length polymorphism (RFLP). The mean number of binding sites/(E) for Yz-1 monoclonal anti-CR1 correlated with the number of sites for polyclonal anti-CR1 that had been determined 2 to 4 yr previously in 18 normal persons (p less than 0.001), 18 patients (p less than 0.001), and 28 relatives (p less than 0.001), indicating that CR1 sites/E was a stable characteristic in all three groups. The mean number of Yz-1 sites/E was 281 +/- 34 (+/- SEM) in 28 probands with SLE and 457 +/- 21 in 93 relatives, both determinations being less than that for 100 normal persons, 553 +/- 21 (p less than 0.002). Thirty-six patients and 51 normal individuals were also assessed for the presence of the 7.4 kb and 6.9 kb HindIII CR1 allelic restriction fragments that correlate with high and low expression, respectively, of CR1 on E. The distribution of patients differed from normal (p less than 0.05), with a smaller proportion being homozygous for the 7.4 kb allele. In addition, the mean numbers of Yz-1 sites/E for patients and relatives who were homozygous (p less than 0.02) and heterozygous (p less than 0.05) for the 7.4 kb allele were significantly lower than those for normal persons matched for the HindIII RFLP, suggesting the existence of additional heritable factors that decrease CR1 expression. The stability over time of the CR1 deficiency among patients, the finding of decreased CR1 number among an expanded group of relatives, the altered frequency among patients of CR1 alleles defined by the HindIII RFLP, and the decreased expression of CR1 on E among patients and relatives compared with normal individuals having the same HindIII RFLP indicate a role for genetic factors in CR1 deficiency in SLE.
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PMID:Deficiency of the C3b/C4b receptor (CR1) of erythrocytes in systemic lupus erythematosus: analysis of the stability of the defect and of a restriction fragment length polymorphism of the CR1 gene. 288 67

Expression of the C3b/C4b receptor (CR1) on erythrocytes is decreased in patients with systemic lupus erythematosus (SLE) compared to normal individuals, and the CR1 antigen is absent from podocytes in severe diffuse proliferate nephritis of SLE. In the present study, we examined the relationship between the number of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes and the occurrence and severity of SLE nephritis, and assessed the expression of CR1 on erythrocytes in non-SLE nephritis and other systemic inflammatory diseases by measuring the binding of 125I-labeled rabbit F(ab')2 and murine monoclonal IgG anti-CR1 antibodies to erythrocytes of normal individuals and patients in a French population. The number of binding sites for monoclonal anti-CR1 antibody on erythrocytes of 116 normal individuals was 743 +/- 22 (mean +/- SEM) with a range of 169-1,333, and the frequency distribution of this number in the population was bimodal. In 112 patients with SLE, the mean number of CR1 sites on erythrocytes was decreased to 62% of the mean for normal individuals (p less than 0.001). No correlation was found between CR1 expression on erythrocytes and the presence or immunohistopathological type of glomerulonephritis in biopsy specimens from these patients. The mean number of CR1 on erythrocytes of 29 patients with non-SLE glomerulonephritis was slightly decreased to 89% of the normal mean (p greater than 0.05), which could not be attributed to glomerular immune complex disease or vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased expression of C3b receptor (CR1) on erythrocytes of patients with systemic lupus erythematosus contrasts with its normal expression in other systemic diseases and does not correlate with the occurrence or severity of SLE nephritis. 294 97

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc). A significant negative correlation was found between the presence of this C1q-binding material and subepithelial electron-dense deposits, suggesting that the presence of this material contributed to the absence of subepithelial immune deposits. Large-molecular-weight C1qSP-binding material was also present, mainly in sera from patients with proliferative lesions. Furthermore, highly positive correlations were found between immune deposits in interstitial blood vessels and peritubular areas, and the concentrations of C1qSP-binding IgG and rapidly sedimenting IgG in density gradient analysis. Overall, these findings are consistent with the hypotheses that circulating immune complexes contribute to the pathogenesis of glomerulonephritis and interstitial nephritis in patients with SLE, and that 6.6S C1q-binding IgG plays a role in the proliferative lesions of lupus glomerulonephritis.
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PMID:Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus. 310 94

The effect of plasma exchange (PE) on blood pressure (BP) in 20 hypertensive patients (9 with mixed cryoglobulinemia, 7 with systemic lupus erythematosus, and 4 with idiopathic glomerulonephritis) was evaluated retrospectively. In each PE 1.5-2.5 L of plasma was replaced with an equal volume of 4% albumin polysaline solution. The frequency of PE was three times per week for the first 2 weeks and twice per week subsequently. Sixteen patients were on hypotensive treatment at the onset of PE. Their systolic/diastolic BP was 171 +/- 4.7/102 +/- 3.0 mm Hg (mean +/- 1 SEM). After 4 weeks, BP decreased to 141 +/- 2.8/89 +/- 2.3 mm Hg (p less than 0.001), although in 10 patients antihypertensive drug therapy had been reduced or discontinued. The most marked decrease of BP occurred after the first week (152 +/- 5.3/92 +/- 2.9 mm Hg), and this decrement correlated remarkably well with pressure levels before PE despite the great heterogeneity of the individual patients (for diastolic BP, r = 0.87, p less than 0.001; for systolic BP, r = 0.60, p less than 0.01). A mild decrease of serum creatinine was observed during PE, but its time course was different from that of BP, and did not correlate with this parameter.
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PMID:Hypotensive effect of plasma exchange in immune complex nephritis. 315 96

A 29-yr-old woman with systemic lupus erythematosus (SLE) was found to have no detectable C3b/C4b receptors (CR1) on her erythrocytes (E) when they were assayed by the binding of rabbit polyclonal and murine monoclonal (Yz-1) anti-CR1. Analysis by two-color fluorescent flow cytometry of CR1 expression on the patient's B lymphocytes that had been stained indirectly with monoclonal anti-B1 and rabbit F(ab')2 anti-CR1 also revealed a marked deficiency of CR1. Total cellular CR1 of neutrophils, assessed by a sandwich radioimmunoassay, was about half that of neutrophils from normal individuals. Because her E had expressed 173 sites/cell 2 yr before, the CR1 deficiency was considered to be acquired and a possible mechanism was sought. Autoantibody to CR1 was measured by a radioimmunoassay in which serum or its fractions were incubated in microtiter wells that had been coated with purified CR1, and binding of immunoglobulin to the wells was quantitated with 125I-labeled goat IgG antihuman F(ab')2. The CR1-specific binding of immunoglobulin from the patient's serum was 19.1 ng/well of the detecting antibody when her E had eight CR1 sites per cell; that of 28 healthy donors was 1.3 +/- 0.5 ng/well (mean +/- SEM), and that of 34 additional patients with SLE was 0.5 +/- 0.3 ng/well. The activity was present also in purified IgG and its F(ab')2 fragment, indicating that the binding of serum immunoglobulin to CR1 was not mediated by C3 fragments. The specificity of the patient's IgG for CR1 was confirmed when pretreatment of the CR1-coated wells with affinity-purified rabbit F(ab')2 anti-CR1 was shown to inhibit by 68% the binding of the IgG. The autoantibody also interacted with CR1 in cell membranes, as assessed by its capacity to inhibit the binding of indirectly fluoresceinated Yz-1 to neutrophils, and, when combined with goat IgG antihuman F(ab')2, to diminish the binding of dimeric C3b to normal E. During the period of the marked deficiency of CR1 the patient experienced an exacerbation of disease activity which was treated with prednisone. Clinical improvement was accompanied by a decrease in the serum concentration of anti-CR1 to levels present 2 yr earlier, and an increase of CR1 to 170 sites/E. The temporal association between high titers of an autoantibody to CR1, absence of CR1 from E, and heightened activity of SLE suggest that the former may have had a role in the other manifestations of the patient's disease.
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PMID:Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus. 401 77

Medical records of patients having unilateral nephrectomies done between 1953 and 1978 at a university hospital were reviewed after 5 to 30 years of follow-up to determine if this procedure causes insidious renal insufficiency. Forty patients (selected from 571) ranging in age from 20 to 72 years met the following criteria for inclusion in the study: subject over 20 years of age at nephrectomy; initial serum creatinine concentration less than 1.6 mg/dL; normal arterial blood pressure (less than 150/90 mm Hg); absence of risk factors for chronic renal disease, eg, systemic lupus erythematosis, diabetes mellitus, chronic glomerulonephritis; an initial and a follow-up serum creatinine level; at least 5 years of follow-up. After a mean follow-up of 11.8 years, paired analysis of changes in serum creatinine concentrations showed insignificant differences between pre- and post-nephrectomy levels (0.19 +/- 0.11 mg/dL +/- SEM). Only one patient had a post-nephrectomy serum creatinine level above 2.0 mg/dL. Six patients (four women, two men) developed hypertension (15%) after uninephrectomy, an incidence of hypertension not greater than that found in the population at large. We conclude that uninephrectomy at ages older than 20 years does not lead to renal insufficiency or hypertension in adult patients with normal prenephrectomy serum creatinine and blood pressure levels.
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PMID:Long-term effect of uninephrectomy on serum creatinine concentration and arterial blood pressure. 403 59

Procainamide (PA) induces the production of a number of autoantibodies in a high proportion of treated individuals and in some a syndrome closely resembling systemic lupus erythematosus. The mechanism underlying this action of PA is unclear. To examine the possibility that PA might induce autoantibody formation by altering normal immunoregulatory mechanisms, the action of this drug on an in vitro model of antibody formation in man was examined. PA was found to augment the generation of immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (PBM) in response to pokeweed mitogen but had no effect on pokeweed mitogen-induced tritiated thymidine incorporation. When purified populations of B and T cells were used, PA enhanced the generation of ISC in B-cell cultures supported by untreated T cells but not by T cells treated with mitomycin C. These results indicate that PA augmented B-cell responses by inhibiting suppressor T-cell activity and not by augmenting helper T-cell or B-cell function. N-Acetyl-procainamide had no effect on the generation of ISC in this system. The effect of PA on concanavalin A (Con A)-induced suppressor cell activity was also examined to determine whether PA altered the generation or expression of suppressor T-cell function. PBM were cultured with 30 microgram/ml of Con A for 48 h to generate suppressor cells. When these were co-cultured with fresh PBM, the number of ISC generated was decreased by 58.1 +/- 3.4% (mean +/- SEM, n = 6). Cells that had been similarly incubated without Con A were not inhibitory. The addition of PA to the Con A-stimulated cultures inhibited the generation of suppressor cells as indicated by the fact that the response of fresh cells co-cultured with the Con A-stimulated cells was diminished by only 27.2 +/- 4.3%. In this system too, N-acetyl-procaimamide had no effect. By contrast, adding PA only to the co-culture of Con A-stimulated cells with fresh PBM had a less marked effect on suppressor cell function. These results indicate that the major action of PA is to inhibit the generation of suppressor T-cell activity. Such an effect may explain the capacity of this agent to induce autoantibody formation in treated individuals.
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PMID:Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro. 621 16

Plasma androgen levels were determined by radio-immunoassay in 19 female patients (aged 14 to 42 years) with systemic lupus erythematosus (SLE). In 11 patients studied in the active phase of the disease, prior to any corticosteroid therapy, mean (+/- SEM) plasma concentrations (ng/ml) of the following androgens were significantly reduced as compared with controls (12 normal women aged 19-37 years): testosterone (0.119 +/- 0.021 vs 0.330 +/- 0.034, p less than 0.001), dihydrotestosterone (0.078 +/- 0.013 vs 0.150 +/- 0.014, p less than 0.01), dehydroepiandrosterone (1.60 +/- 0.16 vs 4.30 +/- 0.50, p less than 0.001), dehydroepiandrosterone sulfate (480 +/- 102 vs 1020 +/- 92, p less than 0.001), and androstenedione (0.69 +/- 0.22 vs 1.45 +/- 0.18, p less than 0.02). In 8 patients studied while in post-therapeutic remission, six months to seven years after corticosteroid withdrawal, plasma concentrations of the same androgens (except androstenedione) were also significantly reduced as compared with controls, although to a lesser degree. In neither of the two patient groups were cortisol and estradiol levels significantly different from controls. Our results suggest that low plasma androgen levels could be a permanent disorder in female SLE patients, at least in severe forms of the disease.
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PMID:[Plasma androgens in women with disseminated lupus erythematosus]. 622 Feb 98

The ability of sera from patients with systemic lupus erythematosus (SLE) to alter the natural killer (NK) cell activity and antibody dependent cell mediated cytotoxicity (ADCC) of peripheral blood mononuclear cell populations from normal donors was determined employing 4-h 51Cr release assays. SLE sera significantly lowered the NK activity of both whole mononuclear cell populations (MN) (26 +/- 3% decrease) (mean +/- SEM) and lymphocyte enriched populations (24 +/- 5%) toward K562 targets when compared to results with sera from normal donors. The continuous presence of serum was not required for this effect since MN effector cells preincubated with sera and then washed also exhibited diminished NK activity. SLE sera decreased only slightly lymphocyte-mediated ADCC to either erythrocyte (human 0 + RBC) or tumor cell (human CEM T lymphoblast) targets. ADCC by isolated monocytes, however, was significantly diminished by SLE sera (54 +/- 5%). These data suggest that in patients with SLE, serum factors may be responsible for alteration of both NK activity and ADCC.
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PMID:Effects of serum from patients with system lupus erythematosus on leukocyte cytotoxicity: modulation of NK activity and ADCC. 666 95

Phytohemagglutinin-stimulated peripheral blood T lymphocytes, plated in agar, are capable of forming discrete lymphoid colonies. In 35 normal subjects, the average number of colonies was 6,020 +/- 351 (SEM). By contrast, in 39 patients with systemic lupus erythematosus (SLE), the mean colony number was 2,774 +/- 384, a value significantly less than controls (P less than 0.001). Normal responses were measured in 5 patients with progressive systemic sclerosis and in 7 of 8 patients with rheumatoid arthritis. Colony growth in SLE showed a strong correlation with disease activity but did not correlate with responses of blood lymphocytes to phytohemagglutinin in suspension cultures, the number of circulating T cells, or serologic abnormalities.
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PMID:Depressed T cell colony growth in systemic lupus erythematosus. 696 51


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