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PubMed1989

Treatment of systemic lupus erythematosus (SLE) with piroxicam (Hotemin-Egis).

Thirty patients suffering from systemic lupus erythematosus (SLE) were treated with daily 20 mgs of piroxicam (Hotemin). The patients were in a mildly active stage of the disease, taking maintenance doses of corticosteroids. The duration of piroxicam therapy was 3 months. Allergy was observed in one case, intolerance (gastrointestinal symptoms, nausea, vomiting) in two; these resulted in the cessation of therapy. Twenty seven patients were on piroxicam therapy for 3 months. Signs of clinical activity diminished, corticosteroid requirement decreased, subjective complaints were reduced. The drug was tolerated. In 3 cases, due to mild water retention, diuretics were given. Gastrointestinal symptoms, transaminase elevation, changes in blood cell counts were not observed during the 3 months period.

Adolescent↗

PubMed1989

Plasma proteinase regulation during disease progression in murine models of SLE.

Analysis of plasma proteinase during disease progression in murine models of systemic lupus erythematosus revealed three different patterns of regulation. Female NZB/W mice exhibited no age-dependent alterations in plasma proteinase activity from 3-9 months of age. Animals at nine months of age exhibited splenomegaly, high titers of serum autoantibodies and evidence of kidney disease, but no disruption of plasma proteinase activity. Male BxSB mice exhibited elevations in plasma proteinase activity as a late-onset (greater than 20 weeks of age) feature of the disease process. The onset of proteinase dysregulation occurred after significant mortality was evident and therefore variables associated with the induction of elevated levels of plasma proteinase activity are not related to early mortality factors. In contrast, female MRL-lpr mice exhibited age-dependent induction of elevated plasma proteinase activity which correlated temporally with the onset of mortality and the previously described reticuloendothelial system activation (Hart, J. Clin. Lab. Immunol., 26, 129). Interestingly, male MRL-lpr mice, which live slightly longer than female mice of the same strain, exhibited a delayed onset of plasma proteinase dysregulation. These results indicate that induction of changes in plasma proteinase regulation during the natural course of disease varies between these three murine models of SLE. Assessment of plasma proteinase regulation in human disease may reveal subpopulations of patients with features analogous to the murine models, which in turn could influence the choice of therapeutic modalities in disease management.

Animals↗

PubMed1988

Human repetitive and unique sequences coexist in a large circulating DNA species found in cryoprecipitates from SLE patients.

Cryoprecipitates from systemic lupus erythematosus (SLE) patients with high levels of anti DNA antibodies show a sharply migrating large circulating DNA species of about 17-20 kb (M. Rieber et al., Clin. exp. Immunol. (1986) 66, 61). We have now used Southern blot analysis of circulating DNA from different individuals to analyse the relative cross-hybridization of circulating DNA from different individuals, as well as their homology with genomic DNA from different species. Molecular hybridization showed significant homology of the various circulating DNA examined, only with human genomic DNA, but limited cross-reactivity among circulating DNA from different individuals. This suggests that the circulating DNA is composed of sequences repeated in human genomic DNA and by specific sequences unique to circulating DNA from some individuals. Our data suggests the possibility of using probes derived from the specific sequences now reported in the circulating DNA, in gene typing and in the analysis of susceptibility to disease.

Base Sequence↗

PubMed1987

Modulation of T3 antigen in systemic lupus erythematosus (SLE).

One of the first steps in the T cell activation is modulation of T3-Ti complex from the cell membrane. This process was studied in patients with SLE by immunofluorescence staining and measured in a cell sorter. The modulation of T3 antigen was impaired in a number of patients. The mitogen-induced proliferation was also decreased in these cases, but decreased blast transformation occurred also with efficient modulation. Pretreatment of normal T lymphocyte with sera from patients with decreased modulation caused only moderate inhibition of T3 antigen modulation. Modulation in vitro was not influenced by steroids.

Antibodies, Monoclonal↗

PubMed1987

Serum steroid hormone levels in systemic lupus erythematosus (SLE).

Dehydroepiandrosterone (D), D sulphate (DS), testosterone (T) and oestradiol (OE2) were determined by radioimmunoassay; cortisol (F) by a spectrofluorimetric method in the serum of 54 female patients with SLE. The values were evaluated in two age groups (32 patients with active ovarian function and 22 in menopause). The serum cortisol, T and DS levels were decreased, and there was no difference in that of free (unconjugated) D and OE2 concentrations compared to normal female subjects.

Adolescent↗

PubMedDate not supplied

SLE and pregnancy.

In patients with SLE in remission pregnancy does not confer a special risk to either the mother or foetus, and immunoregulatory drugs should not be withdrawn prior to a pregnancy where these are required for disease control. Likewise therapy to treat disease flares during pregnancy should not be withheld as the foetus is at comparitively more risk from the effects of the maternal disease than from the small risk associated with therapy. Patients with active disease should be counselled against pregnancy but therapeutic abortion in such patients is only very rarely indicated. High risk groups benefit from close monitoring though the previous obstetric history will not necessarily reflect outcome in subsequent pregnancies. Patients without a previous obstetric history should not be treated prophylactically due to the detection of antiphospholipid antibodies, and the optimum treatment for those with poor histories and aPL is currently being investigated.

Female↗

PubMed1987

A lysine-binding protein in SLE sera inhibits the binding of immune complexes to normal erythrocyte CR1 (complement receptor type 1).

The binding of 125I-labelled immune complexes (IC) to normal human erythrocyte CR1 (complement receptor type 1) by sera from patients with SLE was found to be significantly decreased compared to normal sera. In 13/29 patients, there was an inhibitor which decreased the binding of opsonized IC in normal sera to normal erythrocytes. It was found in each of the nine patients who had clinically active disease. The inhibitor was shown to be a globulin that was labile at 56 degrees C and bound to lysine; low concentrations of tranexamic acid and of lysine abolished the effects of the inhibitor which suggests that it possesses lysine-binding sites: these may block the CR1-binding site on IC opsonized with complement. This inhibitor may decrease the efficiency of IC carriage by erythrocyte CR1.

Antigen-Antibody Complex↗

PubMed1988

Antinuclear antibody-negative systemic lupus erythematosus (SLE) and severe renal involvement: close correlation between disease activity and appearance of circulating anticoagulant.

A 16-year-old girl meeting the criteria for SLE is described. Salient features of the clinical course included active glomerulonephritis with dense subepithelial deposits on electron microscopy, pulmonary embolism, axillary vein thrombosis, arthritis, serositis and fever. Disease activity correlated with the presence of lupus anticoagulant as measured by VDRL and partial thromboplastin time (PTT). Her serum was consistently negative to ANA, anti-DS-DNA, anti-SS-DNA, ENA, anti-Ro, anti-La, and LE cells for the entire 4-year course. She responded remarkably to prednisone and azathioprine. Reappearance of VDRL and elevated PTT preceded exacerbation of disease activity and served as a serological guide for modifying medical treatment.

Adolescent↗

PubMed1988

Monoclonal hybridoma anti-cardiolipin antibodies from SLE mice.

To determine whether the anti-cardiolipin antibodies are identical with the lupus anticoagulant and other antibodies to phospholipids and DNA, we prepared monoclonal hybridoma autoantibodies to cardiolipin from SLE-prone MRL/lpr mice and characterized their specificity. Using a somatic cell hybridization technique, we established three hybridoma clones which produce antibodies to cardiolipin (CAL-1: IgG2b, k, CAL-2: IgM, k and CAL-3: IgM, k). These hybridoma antibodies preferentially reacted with cardiolipin and phosphatidylserine, weakly reacted with phosphatidylinositol, but not with other phospholipids such as phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and VDRL antigen. Two hybridoma anti-cardiolipin antibodies bound to ssDNA and were found to act as the lupus anticoagulant when mixing activated partial thromboplastin time with cephalin. These autoantibodies may prove to be good tools for elucidating mechanisms of thrombosis, thrombocytopenia, fetal loss and other related manifestations found in patients with systemic lupus erythematosus.

Animals↗

PubMed1988

Characterization of circulating immune complexes detected by monoclonal rheumatoid factor and conglutinin radioimmunoassays in SLE nephritis.

By utilizing a monoclonal rheumatoid factor (mRF) and bovine conglutinin (K) in radioimmunoassays, ICs detected in sera of patients with lupus nephritis were partially characterized. The mRF-RIA detected high levels of ICs in 86.9% of patients with active SLE and in only 22.7% of patients with inactive disease. Positive association was observed with clinical scores and significant negative correlation was found with serum levels of C1q, C3 and C4. The mRF-reactive ICs were shown to be cryoprecipitable and analysis by gel filtration through Sephacryl S-300 disclosed a material eluting between IgM and IgG, being dissociated in acidic pH. On the other hand, no association could be demonstrated between levels of ICs detected by K-RIA and clinical activity. Positivity in this assay was only 8.7% and 31.8% for active and inactive groups. Differently from the ICs detected by mRF-RIA, the K-reactive material was not precipitated by 3.5% PEG, nor by centrifugation in the cold, and EDTA did not reduce the binding of IgG to K in positive sera. The reactive IgG in Sephacryl S-300 chromatography eluted in the same position as monomeric IgG both in neutral and dissociating conditions. No C3 could be detected in ICs reactive in both assays.

Antibodies, Monoclonal↗

PubMed1987

Deficiency of C2, the second complement component, in the family of a patient with SLE-like syndrome: the first case of hereditary C2 deficiency in Czechoslovakia.

A family with hereditary C2 deficiency was discovered in Czechoslovakia. The proband is a 47-year-old female with a SLE-like syndrome and zero activity of the classical complement pathway. Functional CH50, C1, C2, and C4 estimations for all family members revealed a homozygous C2 deficiency in both the proband and her elder sister, and several heterozygotic C2-deficient individuals. The defect segregates with haplo-type HLA A25, B18, DR2.

Adult↗

PubMed1987

Antigranulocyte antibodies in patients with systemic lupus erythematosus (SLE).

Antigranulocyte antibodies were studied in patients with systemic lupus erythematosus. The frequency and type of the antibodies were identified with ELISA (Enzyme-Linked Immunosorbent Assay) and MGCT (microgranulocytotoxicity test). To check antibody specificity, a LCT (lymphocytotoxicity test) was used parallel with the above technique. The ELISA proved to be suitable for determining antigranulocyte antibodies. There was a correlation between the serum level of IgG-type antigranulocyte antibodies and granulocytopenia, but the IgM-type antigranulocyte antibodies failed to show a similar correlation. A good parallelism was found between MGCT--a test to be used to determine IgM-type antibodies--and the IgM-type antigranulocyte antibodies determined by ELISA. Of 25 SLE sera, 13 were found positive for antigranulocyte antibodies. LCT was used to examine the presence of HLA antibodies in these sera and 39% of the sera positive for antigranulocyte antibodies appeared to be granulocyte-specific while 61% reacted in the LCT, too.

Adult↗

PubMed1986

Symptomatic secondary Sjögren's syndrome in patients with systemic lupus erythematosus (SLE). Relation to anti-SS-A and anti-SS-B autoantibodies.

The prevalence of symptomatic secondary Sjögren's syndrome in 66 patients with SLE recruited from a defined population in southern Sweden was 59%. In 26 patients (39%) the symptoms were mild and variable, related to disease activity, while in a smaller group (20%) the symptoms appeared to be constant. The latter patients had an increased frequency of thyroid disease and autoantibodies to SS-A. The patients in this group were older, but did not seem to differ in regard to other disease manifestations.

Antibodies, Anti-Idiotypic↗

PubMed1987

Mortality in SLE nephritis.

In a review of 112 patients with SLE nephritis treated between 1976 and 1982, 31 were known to have died. Renal failure (32.2%) was the commonest cause of death. Gastrointestinal haemorrhage (16%), infections (12.8%) and central nervous system involvement (6.5%) were important causes of death. Thirteen out of 17 patients dying in the presence of renal failure had initially presented with renal impairment. Renal biopsies in 16 patients who have died showed diffuse proliferative glomerulonephritis in all except 1 patient, and uraemia was the commonest cause of death in these patients. Pregnancies terminating in abortions were followed by complications in 5 patients. Discontinuation of steroid therapy by patients was followed by complications, and ended in death in 6 patients.

Adult↗

PubMed1986

Novel DNA-protein complex and a large DNA in SLE cryoprecipitates.

Agarose gel electrophoresis of cryoprecipitates from systemic lupus erythematosus (SLE) patients revealed the presence of a slowly migrating DNAse I-sensitive DNA species at the top of the gel. Upon deproteinization, electrophoretic migration was modified favouring the migration of a 17.5 kb DNA fragment. Mixing experiments adding human serum or plasma to a lambda phage DNA digest revealed a DNA-protein interaction shown by an accumulation of high mol. wt polynucleotide at the top of the gels, and a slowed migration of the DNA bands. No comparable effect was observed when serum albumin was added to the lambda DNA digest. Dot hybridization analysis showed preferential reactivity of the 17.5 kb DNA to human DNA, implying its human origin. Our data suggests that most of this high molecular weight DNA exists as a DNA-2 protein complex. Our mixing experiments also suggest the occurrence of an excess of free DNA antibodies. We propose that the DNA-protein association may play a role in the stabilization and immunogenicity of the nucleoprotein complex.

Antigen-Antibody Complex↗

PubMed1987

Idiotypic analysis of myeloma proteins: anti-DNA activity of monoclonal immunoglobulins bearing an SLE idiotype is more common in IgG than IgM antibodies.

The anti-idiotype 3I which recognizes a determinant on kappa-chains of anti-DNA antibodies in SLE patients also recognizes a determinant on kappa-chains of 82/706 myeloma proteins tested. Twenty-nine of these 82 proteins bind to double-stranded DNA, including two monoclonal IgM, one monoclonal IgA, and 26 monoclonal IgG proteins. DNA binding is much more frequent in the IgG than in the IgM myeloma proteins (p less than 0.001), and is also associated with cationic antibody charge. Two-dimensional gel electrophoresis reveals markedly increased charge heterogeneity of both heavy and light chains of the monoclonal IgG as compared with the monoclonal IgM proteins. We postulate that the increased charge heterogeneity of the IgG-associated 3I-reactive kappa-light chains may reflect somatic mutation, and that DNA specificity within the 3I idiotype system arises by somatic mutation of germ-line genes found in normal individuals. DNA binding may be associated with those mutations that give rise to a cationic immunoglobulin charge.

Antibodies, Monoclonal↗

PubMed1985

DNA affinity column chromatography: application in the isolation of distinct antibody populations from SLE sera.

An improved method was developed for purification of anti-DNA antibodies by single-stranded DNA (ssDNA), or double-stranded DNA (dsDNA) affinity column chromatography. The effectiveness of this method was examined by measuring the recoveries and purifications of various monoclonal and polyclonal antibodies. Results showed that this method gave good recoveries and purifications of anti-DNA antibodies. Furthermore, by this method, it was possible to isolate antibody populations with distinct specificities from polyclonal antibodies, as shown by enzyme linked immunosorbent assay (ELISA). Therefore, this method should be useful for characterization of polyclonal antibodies in the sera of patients with systemic lupus erythematosus (SLE) as well as of autoimmune lupus mice.

Animals↗

PubMed1985

Quantitation of anti-RNP and anti-Sm antibodies in MCTD and SLE patients by immunoblotting.

A quantitative immunoblotting assay (QIBA) for the determination of specific antibody titres in human autoimmune sera is described. In this assay, a total HeLa nuclear protein fraction, immobilized on nitrocellulose blot strips, was used as source of antigens and immunoreactive species of autoantibodies were quantitated by an enzyme linked second antibody procedure. Besides being more discriminative, QIBA appeared to be up to 500 times more sensitive than immunodiffusion or immunoelectrophoresis. In this study we used 21 sera from patients with SLE or MCTD for a quantitative analysis of their specific autoantibody content. Within this group, a very diverse spectrum of antibody populations was observed; anti-RNP sera appeared to contain, among others, high tired antibody versus 70K and 31K polypeptides while all (n = 6) anti-Sm sera recognized a 25kD protein doublet. In a follow-up study of two MCTD patients significant flares in specific antibody content could be observed.

Adult↗