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)

An enzyme immunosorbent assay of neopterin and biopterin on a polystyrene microtiter plate has been developed. A conjugate of neopterin or biopterin to bovine serum albumin was used to raise a specific antiserum against neopterin or biopterin in rabbits. An incubation mixture of the antiserum and samples prepared from human serum underwent another antigen-antibody reaction with the hapten fixed on the microtiter plate. The amount of antibody bound to the fixed hapten, which is inverse to the amount of hapten in the sample, was determined by using anti-rabbit IgG-horseradish peroxidase conjugate in a usual manner by measuring absorbance at 490 nm after reaction with o-phenylenediamine and hydrogen peroxide. The minimal detectable amounts of neopterin and biopterin were approximately 0.1 pmol. The specificity of the assay was so high that the assay system for neopterin completely distinguished it from biopterin, as judged from the cross-reaction of 0.002%, and vice versa. The amounts of neopterin and biopterin in human serum determined by the present method agreed well with those determined by high-performance liquid chromatography. We used the present method to determine the concentrations of neopterin in serum from healthy control subjects and patients with cancers and systemic lupus erythematosus; the results were consistent with literature data.
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PMID:Highly sensitive, specific enzyme-linked immunosorbent assay of neopterin and biopterin in biological samples. 139 77

Immunization of BALB/c mice with denatured DNA (dnDNA)-methylated bovine serum albumin (MBSA) complex along with aluminium hydroxide gel as adjuvant, resulted in the induction of anti-DNA antibodies of both IgG and IgE isotypes demonstrable by avidin-biotin micro enzyme-linked immunosorbent assay (ELISA) and solid phase radioimmunoassay (SPRIA), respectively. In contrast to the high levels of IgG2a and IgG2b anti-DNA antibodies observed in SLE-prone autoimmune mice, more than 90% of the anti-DNA antibodies of IgG isotype were found to be of IgG1 subclass. Specificity of both IgG and IgE antibodies which recognized activated DNA, dnDNA and double-stranded DNA but not RNA was established by competitive ELISA and SPRIA inhibition assays. These antibodies cross-reacted with cibacron blue and chondroitin sulfate but not with various other proteoglycans, nucleosides and nucleotides. Passive cutaneous anaphylaxis reaction in rats showed that these antibodies are capable of inducing in vivo degranulation of mast cells in a dose-dependent manner. These studies lend support to the concept that IgE antibodies directed against DNA may mediate mast cell degranulation and thus contribute to immediate-type hypersensitivity phenomena including hives seen in patients with systemic lupus erythematosus and to the localization of IgE-nucleic acid complexes.
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PMID:Induction of anti-DNA IgG and IgE antibodies in BALB/c mice. 141 1

A patient with connective tissue disease presenting with both protein-losing enteropathy and pancreatic involvement is reported. A 52-year-old female was admitted because of mild epigastralgia, anasarca and ascites. Serum albumin, transferrin and zinc, showed low levels. An Upper G.I. series and endoscopy showed thickened folds of the duodenum and the jejunum. Biopsy specimens revealed lymphangiectasia in edematous villi. 99mTc-labeled human serum albumin scintigram showed abnormal radioactivity in the small intestine 90 minutes after intravenous injection, indicating protein-losing enteropathy. Hypoalbuminemia was ameliorated by glucocorticoid therapy, but recurred twice when glucocorticoid treatment was tapered. Hypoalbuminemia has not occurred since intestinal lymphangiectasia was improved with glucocorticoid treatment. Levels of elastase 1 and lipase were high in serum and ascites on admission. Endoscopic retrograde pancreatogram showed no abnormalities. Serum pancreatic enzymes were also ameliorated by glucocorticoid therapy, but slightly high levels continued for about one year and a half. This case might have been diagnosed as systemic lupus erythematosus although mixed connective tissue disease was also suspected. There are few reports of protein-losing enteropathy and pancreatic involvement associated with connective tissue diseases. Protein-losing enteropathy and pancreatic involvement were ameliorated with glucocorticoid treatment, suggesting participation of immunological mechanisms.
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PMID:Protein-losing enteropathy and pancreatic involvement in a case of connective tissue disease. 157 30

Solubilization of preformed bovine serum albumin (BSA) rabbit anti-BSA complexes in serum with kinetic analysis, haemolytic complement function, complement proteins C1q, C4, C3 and complexes containing C1 inhibitor (C1 INH-C1r-C1s-C1 INH) were serially investigated in relation to disease activity in 25 patients with systemic lupus erythematosus (SLE). Clinical assessment of disease activity was expressed using a validated global index (SLEDAI). Markedly decreased capacity to solubilize immune complexes in serum was mainly found in sever disease. By serial analysis, evidence of fairly persistently impaired classical pathway function was found in most of the patients. In partial contrast, impaired alternative pathway function was more clearly associated with active severe disease. Immune complex solubilization during short incubation (5-10 minutes) correlated with classical and alternative pathway-mediated haemolysis. Solubilization during long incubation (40 minutes) was correlated with haemolytic alternative pathway function. In some patients gradual impairment of solubilization during short incubation, and reduced classical pathway haemolytic activity were detectable 2-4 months before clinical manifestations prompted therapeutical intervention. SLEDAI was negatively correlated with solubilization during prolonged incubation (40 minutes) and with haemolytic alternative pathway function, further emphasizing involvement of the alternative pathway in severe disease. The findings emphasize the importance of impaired complement function due to complement activation in SLE. Assays for immune complex solubilization or other complement functions appear to be useful for monitoring disease activity in SLE.
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PMID:Kinetic analysis of immune complex solubilization: complement function in relation to disease activity in SLE. 158 69

The effects of 10% fetal calf serum (10% FCS), 10% adult bovine serum (10% ABS) and 1% bovine serum albumin (1% BSA) buffers on the reactivity of samples with or without IgM anticardiolipin antibodies (ACA IgM) were studied on cardiolipin-coated wells (target wells) and cardiolipin-free wells (control wells) in an ELISA test. With 1% BSA, target well reactivity was very low for samples containing ACA IgM. The 10% FCS induced a moderate but significant binding of polyclonal IgM on target wells particularly in the case of IgM hypergammaglobulinemia. With 10% ABS, whatever the IgM serum level, this non-specific binding did not occur on the solid phase either in the presence or in the absence of cardiolipin. Using 10% ABS, the study of 35 SLE sera showed that non-specific binding of IgM on control-wells occurred only with ACA IgM positive samples. Thus with the use of 10% ABS, we propose that subtraction of control well from target well values must not be performed for the detection of ACA IgM. The significance of cardiolipin-free well IgM reactivity of ACA IgM positive sera is discussed.
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PMID:Methodological approach for the detection of IgM anticardiolipin antibodies. 158 79

Intravenous immunoglobulin (IVIG) therapy has been used not only as replacement treatment for immunodeficiency, but also as treatment of autoimmune diseases, specifically Kawasaki disease, systemic juvenile arthritis and juvenile dermatomyositis. In Kawasaki disease, IVIG reduces the incidence of coronary artery abnormalities, as well as rapidly improving clinical and laboratory variables such as fever and rash, platelet count, white blood cell count and serum albumin. Furthermore, a single high dose of 2 g/kg is as effective as 400 mg/kg x 4 days. In systemic juvenile arthritis, followup of at least one year demonstrated that monthly treatment with IVIG resulted in improvement of systemic disease in 10/11 patients, allowed for cessation of prednisone treatment in 7/8 patients and significant improvement of arthritis in 8 patients. In juvenile dermatomyositis, we report 2 uncontrolled trials of IVIG treatment that resulted in significant clinical improvement and steroid-sparing. In contrast, IVIG treatment of systemic lupus erythematosus (SLE) resulted in improvement in 3 patients, but exacerbation or new onset of renal disease in 3 patients. Overall, our report demonstrates that IVIG has been effective both in a controlled trial in Kawasaki disease and in uncontrolled trials in systemic juvenile arthritis and juvenile dermatomyositis. We suggest that IVIG should be used cautiously in SLE.
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PMID:Intravenous immunoglobulin therapy: magic or black magic. 801 61

A systematic study has been carried out to investigate the role of immunoglobulin isotype, epitope density, and antigen/antibody ratio on the capacity of immune complexes to activate the classical and alternative pathways of human complement and for the complexes subsequently to bind to erythrocyte C3b-C4b receptors (CRI). For this purpose, a series of chimaeric monoclonal anti-NIP antibodies was used, which all shared the same combining site but had different human constant domains. Antigen epitope density was varied by coupling different numbers of NIP hapten molecules to bovine serum albumin. All three parameters affect complement fixation. In general, complement activation is better in antibody excess and at equivalence than it is in antigen excess, and better at high epitope density than at low epitope density, although the effects are variable for different immunoglobulin isotypes and for the two pathways. It has been confirmed that IgG1 and IgG3 are good activators of the classical pathway and are tolerant to variations in both epitope density and antigen/antibody ratio. IgG4 and IgA do not activate the classical pathway in any circumstances. IgG2 activates the classical pathway only at high epitope density and at equivalence or antibody excess. IgM activates the classical pathway well only at the higher epitope densities and at equivalence or antibody excess but, in addition, shows an interesting and unexpected prozone phenomenon where immune complex in antibody excess inhibits complement activation by the classical pathway. The results of the alternative pathway activation are strikingly different. IgA is by far the best activator of the alternative pathway and is relatively tolerant to epitope density and to antigen/antibody ratio. IgM, IgG1 and IgG3 do not significantly activate the alternative pathway in any circumstances. IgG2 is the best IgG subclass for alternative pathway activation but requires high epitope density and equivalence or antibody excess. Binding to CR1 in general parallels the amount of complement fixed independent to the pathway by which it is fixed. However, IgG1 and IgG3 complexes in antigen excess activate complement well but bind poorly to CR1. Nascently formed complexes seem to bind complement in a way that is similar to that bound by preformed complexes, but are then less able to bind to red cell CR1. These observations help to explain the pathogenesis of complement activation in various autoimmune and immune complex diseases such as systemic lupus erythematosus, autoimmune thyroiditis and others.
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PMID:The effect of antibody isotype and antigenic epitope density on the complement-fixing activity of immune complexes: a systematic study using chimaeric anti-NIP antibodies with human Fc regions. 170 67

Clinical and pathological findings were studied in 23 male patients with lupus nephritis who were followed up for a period of 41 +/- 36 months after renal biopsy. Age at renal biopsy was 31 +/- 14 years and 19 patients (83 per cent) were between 15 and 50 years old. C3 and C4 levels were below normal in 23 (100 per cent) and 16 (70 per cent) respectively, CH50 was less than 25 u/ml in 67 per cent, and antinuclear and anti-DNA antibodies were found in 87 per cent and 82 per cent respectively. Serum albumin level increased from 2.9 +/- 0.8 g/dl to 3.7 +/- 0.8 g/dl during the follow up period (p less than 0.01), while urinary protein decreased from 2.0 +/- 2.3 g/day to 1.4 +/- 2.5 g/day. There was a significant improvement in the degree of haematuria (p less than 0.01), but serum creatinine levels showed no change (mean 1.5 mg/ml). Active proliferative lupus nephritis of moderate or severe degree was observed in 65 per cent of patients at the initial biopsy. A trend to regression in this activity was seen in most serial biopsies, but the chronicity index showed a slight increase. These data demonstrate that systemic lupus erythematosus in males, in comparison to our previous report of the disease in female patients, is accompanied by more active nephritis, but that it follows a benign course with therapy.
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PMID:Study of lupus nephritis in males. 180 38

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

Autoantibodies arising in (NZB x NZW)F1 (B/W) mice during the lupus-like syndrome were studied and compared to natural antibodies present in normal mice. The antibody activities were tested in sera, circulating immune complexes (CIC) and kidney eluates, using an enzyme immunoassay against a panel of self and non-self antigens: actin, myosin, tubulin, DNA, myoglobin, spectrin and trinitrophenylated bovine serum albumin (TNP/BSA). In the B/M mouse sera, IgM antibodies reacting with all the panel of antigens (PAg) and comparable to those of normal mice, increased moderately from 5 to 9 months and markedly during the last stage preceding death (10 months), when particularly high levels of anti-DNA, anti-tubulin and anti-myoglobin antibodies were noted. Polyreactive IgM antibodies present in CIC were moderately increased while those present in complexes deposited in kidneys were strongly enhanced after the 8th month. IgG antibodies showed an early increase (2 months) in B/W sera for anti-TNP activity, which remained more or less constant until death, while a later (5-6 months) and greater increase of activity, mainly directed against DNA but also against the other antigens of the panel, was observed. In CIC, IgG, mainly anti-DNA but also anti-TNP, were enhanced at the end of the disease while at the same time IgG reacting with all the PAg were found in kidney deposits. Isolation of antibodies from sera on a DNA-immunoadsorbent demonstrated that eluted IgM reacted with all the PAg but mainly with DNA, while IgG reactivity was more restricted to DNA and to a lesser degree to TNP. The D23 idiotype, characteristics of natural polyspecific antibodies, was expressed on IgM and IgG autoantibodies from B/W mice and was enhanced, particularly in kidneys, at the end of the disease. These results demonstrate that natural antibodies are a part of the population of increased autoantibodies in this disease and could participate with IgG anti-DNA antibodies in lupus.
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PMID:Comparison of natural antibodies to autoantibodies arising during lupus in (NZB x NZW)F1 mice. 188 82


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