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)

Anti-U1RNP antibodies occur in patients with mixed connective tissue disease (MCTD), systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other ill-defined connective tissue diseases. To associate the isotypes of anti-U1RNP antibodies with the diagnosis of the disease, namely SLE or MCTD, sequential sera of patients positive for anti-U1RNP antibodies by counterimmunoelectrophoresis (CIE) (32 with SLE, 35 with MCTD) were tested for IgG and IgM anti-U1RNP antibodies by enzyme-linked immunosorbent assay (ELISA) using affinity-purified U1snRNP complexes. Results from ELISA were confirmed by RNA precipitation. IgG RNA precipitation of HeLa cellular extracts was performed using the bulk of the IgG fraction removed from each serum after binding to protein A-Sepharose beads. IgM RNA precipitation was carried out on the IgM fraction of the serum bound to protein A-Sepharose-rabbit anti-human IgM immune complexes. RNAs were electrophoresed in 10.5% acrylamide-7 M urea gels and detected with the silver stain. ELISA showed that all sera were positive to IgG anti-U1RNP, while 12 of the 35 MCTD and 21 of the 32 SLE patients possessed IgM anti-U1RNP (P < 0.025). IgM anti-U1RNP reactivity was found during the follow-up in 20% of 44 sera from 17 MCTD patients and 68% of 112 sera from 23 SLE patients (P < 0.0001). IgG from all the sera precipitated U1RNPs. Eight of the MCTD sera also precipitated U2RNPs and 14 of the SLE sera U2 and/or U4/U6, U5 RNPs. IgM from MCTD sera did not precipitate URNPs, while IgM from SLE sera precipitated predominantly U1RNPs. These data suggest that IgM anti-U1RNP antibodies occur predominantly in patients with SLE. The occurrence of IgG anti-U1RNP without IgM is more frequent in MCTD.
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PMID:Predominance of IgM anti-U1RNP antibodies in patients with systemic lupus erythematosus. 867 May 73

The evidence supporting the use of long-term IVIG therapy to induce remissions in SLE is unimpressive. The single extant clinical study used an open-label design with 12 patients, no placebo control, and questionable statistical methodology. The lack of definitive clinical studies, however, is tempered by case reports documenting significant improvement and apparent lack of toxicity in patients with SLE treated with IVIG. Standard first-line therapy of active SLE should consist of nonsteroidal antiinflammatory drugs, followed by low-dose corticosteroids and antimalarial compounds. Second-line therapeutic alternatives are the cytotoxic agents methotrexate, azathioprine, or cyclophosphamide. IVIG's primary advantage over these conventional therapies is that, unlike immunosuppressant and cytotoxic drugs, IVIG has not been reported to increase the risk of opportunistic infections. Additionally, IVIG obviates the ovarian/testicular toxicity, hemorrhagic cystitis, and carcinogenicity caused by cyclophosphamide. However, IVIG therapy is extremely expensive. (Approximate average wholesale price is $1800 per dose for a 70-kg patient). Thus, IVIG treatment consisting of 0.4 g/kg/d for 5 consecutive days on a monthly basis should be reserved for patients with active SLE resistant to the first- and second-line therapies. While IVIG-induced acute renal failure is considered rare, the serious nature of this adverse event warrants close monitoring of blood urea nitrogen and serum creatinine during and several days after treatment. Preexisting renal dysfunction should be considered a relative contradiction. Further double-blind multicenter trials are warranted to determine the long-term safety, efficacy, and cost/benefit ratio of using IVIG in SLE.
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PMID:Intravenous immune globulin for inducing remissions in systemic lupus erythematosus. 903 28

Despite commonly applied clinical criteria, the early diagnosis of rheumatoid arthritis (RA) often remains difficult, thus delaying on suitable early treatment. In search for a test furthering the early and reliable diagnosis of RA, we have screened for novel disease specific autoantibodies. To this end proteins were isolated from synovial membranes and other tissues following a special protein purification protocol, and these were separated electrophoretically. Western blots were then used to screen sera of RA patients and of individuals suffering from other rheumatic diseases for antibodies to any of these proteins. The most prominent RA specific immunoreaction was with a 68k antigen, occurring in 110 of 167 RA patients (sensitivity is 66%). The antibody could also be identified in seronegative RA patients but not in healthy individuals (55 tested), in only 1 SLE patient of a group of 98 patients with other rheumatic diseases and in 1 out of 22 HIV patients, resulting in a specificity of 99%. Moreover, the anti-68k antibody could be correlated with a more severe course of RA. 13 out of 20 anti-68k positive RA patients (58%) had subcutaneous nodules, while only 2 out of 11 anti-68k negative (20%) did. The mean sedimentation rate of these antibody positive patients was 51 mm/h and 26 mm/h for the negative respectively. The 68k antigen was shown to be present in all human tissues investigated and is probably ubiquitously expressed. It is either located in the endoplasmatic reticulum or cytoplasm or both. Its isoelectric point is 5.1. It proved to be O-glycosylated and contains only one or a few sugar residues as the untreated and the deglycosylated antigen identical electrophoretical mobilities. The patient derived anti-68k antibodies were directed against the sugar residue: deglycosylation of the antigen completely abolished its immunoreactivity. N-acetylglucosamine competes with the antibody for binding the 68k antigen. The antigen physicochemical data of the 68k antigen argue against identity with one of the autoantigens in this molecular mass range already known to be associated with RA or other autoimmune diseases. It is neither identical to the 62k human antigen (EBNA-1) nor to RA33 (A2hnRNP), the 50k Sa antigen or the Hsp70 class of heats-hock proteins. It is argued that the particular method of protein purification applied in combination with separation via SDS-PAGE in the presence of urea, made it possible to detect a hitherto unidentified antigen. Considering the striking disease specificity of the anti-68k antibody it is now worthwhile to look for corresponding autoreactive T cells in order to analyse its role in the pathogenesis of RA.
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PMID:[RA-specific autoantibodies against a 68k antigen]. 923 11

We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.
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PMID:A novel antifolate, MX-68, inhibits the development of autoimmune disease in MRL/lpr mice. 925 May 91

MRL/MpJ-Fas(lpr) (Fas(lpr)) mice develop a rapidly fatal form of systemic autoimmune disease characterized by glomerulonephritis and vasculitis similar to severe cases of systemic lupus erythematosus in humans. To evaluate the requirement for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of tissue injury in this model, we created ICAM-1-deficient MRL/MpJ-Fas(lpr) (ICAM-1/Fas(lpr)) mice. ICAM-1 deficiency resulted in a striking improvement in the survival of Fas(lpr) mice (median +/- SEM survival of Fas(lpr) = 26 +/- 1.7 vs ICAM-1/Fas(lpr) = 47 +/- 2.4 wk, p < 0.0001) and the increased survival was associated with delayed elevations of blood urea nitrogen levels in the ICAM-1/Fas(lpr) mice. Histologic examination of the ICAM-1/Fas(lpr) mice revealed an overall reduction in glomerular disease and a significant reduction in vasculitis in the kidney, lung, skin, and salivary glands when compared with Fas(lpr). These findings indicate that ICAM-1 plays a major role in development of glomerular and vascular injury in Fas(lpr) mice.
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PMID:Intercellular adhesion molecule-1 deficiency protects MRL/MpJ-Fas(lpr) mice from early lethality. 925 74

We evaluated the preventive effects of a novel nonpolyglutamatable antifolate, MX-68, on two experimental murine models of systemic lupus erythematosus (SLE); NZBxNZW F1 (BWF1) mice and chronic graft-versus-host disease (GVHD) mice, in comparison with classical antifolate methotrexate (MTX). The oral administration of 2 mg/kg MX-68, three times a week from 12 to 40 or 60 weeks of age, significantly delayed the onset of proteinuria and prolonged the life-span of BWF1 mice. The elevation of serum blood urea nitrogen (BUN) and cholesterol levels resulting from the development of lupus nephritis was also inhibited. However, MX-68 did not suppress the increase of serum anti-DNA or anti-TNP antibodies or total IgG isotype (IgG1, IgG2 and IgG3) levels. In chronic GVHD mice, MX-68 given three times a week from the day of first cell injection, for 9 weeks, dose-dependently delayed the appearance of proteinuria. The elevation of BUN and cholesterol levels was also inhibited. Furthermore, in the 4 mg/kg MX-68 group, the production of IgG anti-DNA and anti-TNP antibodies was significantly inhibited, but this was not observed in the 2 mg/kg MX-68 and the 4 mg/kg MTX groups. These beneficial effects of MX-68 were much greater than those of MTX in both models. These results suggest that MX-68 might be a more useful drug for the treatment of SLE.
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PMID:Preventive effect of a novel antifolate, MX-68, in murine systemic lupus erythematosus (SLE). 927 76

We treated a 31-year-old woman with systemic lupus erythematosus, renal failure with nephrotic syndrome, and a long-standing seizure disorder, who developed severe hyperammonemia with a fatal outcome. Blood chemistry examination did not indicate liver disease, and amino acid concentrations did not suggest a defect in the urea cycle. Discontinuation of anticonvulsant treatment with valproic acid (VPA) failed to bring about improvement. We speculated that hyperammonemia in this case was induced by VPA, and the existence of other underlying factors, including the administration of aspirin and cimetidine, hypoalbuminemia, and renal failure might elevate the concentration of the serum free fraction of VPA.
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PMID:Fatal hyperammonemia in a patient with systemic lupus erythematosus. 974 59

We evaluated the effect of paclitaxel on the severity of autoimmunity in the murine model of systemic lupus erythematosus (SLE), NZB x NZW F1 mice. Fifteen 20 week old (NZB x NZW) F1 female mice were given a dose of 10 mg/kg paclitaxel by the intraperitoneal route on three alternate days followed by 7.5 mg/kg on three additional alternate days. This pattern of treatment was repeated every 4 weeks for a period of 28 weeks. 20 control mice were injected intraperitoneally with an equal volume of the vehicle used. Serum anti-double stranded DNA (dsDNA) antibody titers and the blood urea nitrogen (BUN) were significantly diminished in the paclitaxel treated group compared to the vehicle treated group. While the onset of proteinuria appeared to be delayed in the experimental group, the difference was not significant. Survival rate improved significantly in paclitaxel treated group (p = 0.04 by log-rank test). These results suggest that paclitaxel is beneficial in the suppression of autoimmunity in this strain of mice by reducing the anti-dsDNA antibody titer and the BUN, prolonging survival.
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PMID:Paclitaxel reduces anti-dsDNA antibody titer and BUN, prolonging survival in murine lupus. 984 98

Pulse therapy with methylprednisolone (Solu-Medrol, Upjohn), 1000 mg daily over three successive days, was administered to patients in two randomized groups of 14 patients in each (23 patients with systemic lupus erythematosus, 5 with rheumatoid arthritis). In one of the groups the drug was taken per os, the other received it intravenously. There was no significant difference between the two groups in terms of clinical effectiveness and incidence of side effects However, the time-related course of such indices as erythrocyte sedimentation rate, the level of leukocytes, of total protein, urea, the blood antioxidant potential, permeability of erythrocytic membranes and capillary and tissue barrier proteinuria as well as the content of immune complexes in the arterial and venous blood was more striking with per os intake. Of the 14 patients, 11 demonstrated short-continued asymptomatic 35% rise in the activity of alaninaminotransferase.
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PMID:[A comparative evaluation of the efficacy of peroral and intravenous pulse therapy with methylprednisolone in rheumatic diseases]. 1005 Apr 56

Needle biopsies of kidney were done in 35 cases of systemic lupus erythematosus (SLE) with renal lesions. The lupus nephritis were classified according to WHO classification and were correlated with response to therapy and prognosis. Detailed clinical features, routine haematological, biochemical tests (e.g., serum urea, creatinine, total protein and albumin, cholesterol, etc), examination of urine (degree of proteinuria and cells) and occurrence of various auto-antibodies e.g., antinuclear antibody (ANA), anti double stranded DNA (anti DsDNA) by enzyme immunoassay (EIA) method, LE cells and rheumatoid factor (RF) were studied in all cases. Clinically hypertension was present in 19 (54.3%) cases and nephrotic range of proteinuria was detected in 20 (57.2%) cases. ANA was found in 31 (88.5%) cases, anti DsDNA 24 (68.5%) and LE cells were detected in 25 (71.5%) cases. RF was detected in 2 (5.7%) cases. Histologically the most frequent lesions were class IV occurring in 15 cases (42.8%) with initial complete remission achieved only 4 cases by immunosuppressive therapy. Active lesions were also most frequent in this class. Class III lesions were found in 8 (22.8%) cases with 6 cases had complete remission. The best prognosis was noted in class II cases with 4 out of 5 (14.3%) cases had complete remission. Class V lesions were found in 6 (17.2%) cases with complete remission achieved in 3 cases. Only one patient presented with class VI lesion. RF positive cases had milder renal lesions.
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PMID:Clinicopathologic study of lupus nephritis. 1006 81


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