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PubMed1982

SLE retinopathy: evaluation by fluorescein angiography.

Fifty-two patients with systemic lupus erythematosus (SLE) were examined by fluorescein angiography, and retinopathy was detected in 15. Three patterns of retinopathy were discerned: 4 patients had disc vasculitis, 6 had multiple cotton-wool spots, and 5 had a normal fundal appearance but fluorescein leakage on angiography. One patient had arterial occlusive disease with retinal neovascularisation and another had extensive venous disease. With 3 exceptions retinopathy was found only in patients with active SLE. No association was discovered between retinopathy and cerebral disease; in particular, fluorescein angiography did no assist the diagnosis of mild cerebral lupus.

Adult↗

PubMed1983

A new specific assay for the detection of DNA immune complexes: its relevance in SLE.

Double-stranded DNA immune complexes (DNA-ICs) were assayed by millipore filtration and deoxyribonuclease digestion in 40 patients with both active and inactive systemic lupus erythematosus (SLE). The assay is superior to the double-stranded DNA antibody (ds ADA) as an indicator of active disease, and, when combined with the total haemolytic complement (CH50) and ds ADA levels it increases the prediction of the relative risk of active disease. A good correlation between actual levels of DNA-ICs and the degree of activity was also shown. We conclude that measurement of DNA-ICs is of value as an additional monitor in the assessment of activity in SLE.

Adolescent↗

PubMed1984

Effects of immune complexes from SLE patients on human monocyte locomotion and Fc receptor function.

The effect of immune complexes (IC) isolated from systemic lupus erythematosus (SLE) sera with polyethylene glycol and gel filtration on the chemotaxis and Fc receptor function of healthy monocytes was examined. Even at a low protein concentration (1 microgram/ml = 1 mg/l) ICs inhibit monocyte chemotaxis. ICs from patients with SLE nephritis are more inhibitory than ICs from patients without renal disease. The inhibitory effects of ICs on monocyte chemotaxis and Fc receptor activity are similar, suggesting a relationship between the chemotactic and Fc receptor function of monocytes. Analysis of the ICs by enzyme-linked immunoassay showed no correlation between the quantity of IgG, C3, and anti-DNA in the IC samples and their effects on monocyte function.

Antibodies, Antinuclear↗

PubMed1986

Complement fixation by anti-dsDNA antibodies in SLE: measurement by radioimmunoassay and relationship with disease activity.

We have developed a sensitive, solid phase radioimmunoassay (RIA) to quantify the amount of complement (C') fixation by anti-double-stranded DNA (anti-dsDNA) antibodies and have studied sera from 48 patients with systemic lupus erythematosus (SLE). 46% of the patients were positive in this assay. There was no correlation with serum C' levels, and only weak correlation with anti-dsDNA activity as measured by a solid phase RIA. An association was shown between positive values for C' fixation by anti-dsDNA antibodies and the presence of active lupus (p less than 0.01); there was a similar association with the presence of active renal disease in those patients with raised DNA binding (p less than 0.01). Our results suggest that quantitative measurement of C' fixation by anti-dsDNA antibodies may provide information about the pathogenicity of such antibodies in patients with SLE and be a better guide to potential end organ damage than the conventional measurement of DNA binding.

Antibodies, Antinuclear↗

PubMed1987

Unusual cranial and abdominal computed tomographic (CT) scan appearances in a case of systemic lupus erythematosus (SLE).

A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment, presenting with abdominal symptoms and signs. On this occasion an abdominal CT scan showed distended and oedematous loops of bowel attributed to an underlying vasculitis. This case illustrates novel CT scan appearances in two systems involved in SLE.

Adult↗

PubMed1980

Antibody to synthetic poly dAT: correlation with antibody to native DNA and specificity for SLE.

Antibodies to synthetic 3H-poly dAT have the advantage over antibody to native DNA in that they have a higher degree of specificity for systemic lupus erythematosus (SLE). This is because poly dAT eliminates the problem of measurement of single stranded antibodies that are not specific for any one condition but which may be detected by native DNA preparations which usually contain single stranded regions. The overall degree of correlation between the two antibodies is good in SLE. Antibodies to poly dAT correlate well with clinical evidence of disease activity but in this study were not particularly associated with the presence of renal disease.

Antibodies↗

PubMed1986

High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE.

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.

Autoantibodies↗

PubMed1983

Complement components, C1 activation and disease activity in SLE.

Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.

Adolescent↗

PubMed1997

Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors.

We have previously demonstrated that experimental expression of the polyomavirus transcription factor T-antigen has the potential to induce anti-DNA antibodies in mice. Two sets of independent evidences are presented here that demonstrate a biological relevance for this model. First, we describe results demonstrating that mice inoculated with T-antigen-expressing plasmids produced antibodies, not only to T-antigen and DNA, but also to the DNA-binding eukaryotic transcription factors TATA-binding protein (TBP), and to the cAMP-response-element-binding protein (CREB). Secondly, we investigated whether polyomavirus reactivation occurs in SLE patients, and whether antibodies to T-antigen, DNA, and to TBP and CREB are linked to such events. Both within and among these SLE patients, frequent polyomavirus reactivations were observed that could not be explained by certain rearrangements of the noncoding control regions, nor by corticosteroid treatment. Linked to these events, antibodies to T-antigen, DNA, TBP, and CREB were detected, identical to what we observed in mice. Antibodies recognizing double-stranded DNA were confined to patients with frequent polyomavirus reactivations. The results described here indicate that cognate interaction of B cells recognizing DNA or DNA-associated proteins and T cells recognizing T antigen had taken place as a consequence of complex formation between T ag and DNA in vivo in the context of polyomavirus reactivations.

Adrenal Cortex Hormones↗

PubMed1992

Monoclonal autoantibodies to cardiolipin derived from SLE mice.

The objective of this study was to clarify the specificity of anticardiolipin antibodies (aCL). Eighteen monoclonal hybridoma aCL from systemic lupus erythematosus (SLE)-prone MRL/Mp-lpr/lpr mice were established, and the reactivity of monoclonal aCL to phospholipids, DNA, nuclei of human epithelial cells, platelets, vascular endothelial cells, heparin, protein C and thrombomodulin was examined. All the 18 monoclonal aCL reacted with phosphatidylserine and some showed reactivity to phosphatidylinositol and phosphatidylcholine. Six of 16 monoclonal aCL were demonstrated to have the property of lupus anticoagulant. Monoclonal aCL were classified into three categories, in terms of DNA-binding specificity. Ten of 18 aCL had characteristics of antinuclear antibodies. Six of 11 aCL reacted with platelets. Three of 18 aCL were bound to vascular endothelial cells and to heparin. No monoclonal aCL reacted with protein C or thrombomodulin. Therefore, the conclusion was made that monoclonal aCL from SLE mice showed a polyspecific nature.

Animals↗

PubMed1993

Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients.

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.

Adolescent↗

PubMed1993

Detection of anti-phospholipid and anti-DNA antibodies and their idiotypes in newborns of mothers with anti-phospholipid syndrome and SLE.

The titers, isotypes and idiotypes of antiphospholipid and anti-dsDNA antibodies were determined in seven pairs of mothers with antiphospholipid syndrome (APLS) and their offspring, in 11 pairs of SLE mothers and their matched infants and in seven respective pairs of healthy subjects. In addition, maternal as well as fetal sera were evaluated for the presence of anti-SSA (Ro), anti-SSB (La) and anti-70 kd RNP autoantibodies. In the sera from APLS patients, as well as in the sera from their offspring, the mean antibody titer of IgG aCL was found to be significantly higher then the corresponding value in the control group (P < 0.01). Highly significant increased titers of IgG anti-DNA antibodies were found in the sera of SLE mothers and their matched offspring (P < 0.0008). The prevalence of anti-SSA, anti-SSA, and anti-70Kd RNP antibodies was lower then that of antiphospholipid and anti-dsDNA antibodies. Only one of the respective offspring had increased levels of these antibodies. The quantity of maternal antibodies transferred to the fetus was depended on their concentration in the maternal circulation, as well as on their type and specificity. Follow-up of newborn sera showed a progressive decrease in the antiphospholipid antibody titers during 3 months. After 6 months it was undetected. Our results point to a transplacental transfer of aCL and anti-DNA antibodies, a phenomenon which is not necessarily associated with respective clinical manifestations, in contrast to the classical humoral mediated autoimmune diseases (e.g. myasthenia gravis).

Adult↗

PubMed1995

Penicillium marneffei infection in a patient with SLE.

We describe a patient with SLE who was infected by the fungus Penicillium marneffei. She was initially misdiagnosed as having disseminated tuberculosis. The correct diagnosis was finally made by bone marrow culture and she responded to a prolonged course of amphotericin B, flucytosine and itraconazole. The clinical presentation and histology of penicilliosis are very similar to those of Mycobacterium tuberculosis. In Southeast Asia, penicilliosis should be considered as a differential diagnosis in patients with SLE who present with fever and lymphadenopathy.

Adult↗

PubMed1995

Research methods for investigating causal relations between SLE disease variables and psychiatric symptomatology.

People with systemic lupus erythematosus (SLE) frequently experience psychiatric problems. Some researchers and clinicians presume that these psychiatric problems are a direct manifestation of the disease, while others suggest that psychosocial and environmental factors have greater etiological significance. The majority of the studies addressing these issues in patients with SLE are too methodologically limited to make confident conclusions regarding etiology. More methodologically sound research in this area is needed. This article describes some of the limitations in past research in the areas of sampling, measurement, research design, data analyses and data presentation. Suggestions for improved methodology in future research are offered.

Humans↗

PubMed1995

Factors associated with mood and mood disorders in SLE.

This study examines the relative contribution of factors associated with anxious and depressed mood, and clinical anxiety and depression in SLE. Eighty sequentially consenting patients attending a rheumatology outpatient clinic were assessed on measures of anxiety and depression; disease activity; presence of autoantibodies; neuropsychological performance; and psychological and social factors. Mood and mood disorders were found to be unrelated to measures of disease activity but were found to be associated with psychological and social factors. These findings emphasise the importance of psychosocial factors in attempts to understand mood and psychological distress in SLE.

Adolescent↗

PubMed1995

Dual inhibitory and stimulatory activities in serum from SLE patients and lupus mice that regulate the proliferation of an IL-2-dependent T cell line.

In serum and plasma from SLE patients, we have detected elevated levels of factors which regulate proliferative responses of CTLL cells to IL-2. Serum samples containing these factors have dose-dependent dual inhibitory and stimulatory activities on the proliferation of this IL-2-dependent T lymphocyte cell line. At high concentrations, the serum factors inhibit the proliferative responses of CTLL cells to IL-2. At low concentrations, they synergise with IL-2 stimulating the growth of cells. Similar inhibitory activity, but with lower titre, was also found to be elevated in sera of some MRL/lpr mice, an animal model of SLE. Functional characterisation of the serum factors shows that: (1) the inhibitory activity cannot be neutralised by exogenous IL-2; (2) the stimulatory activity is not due to the presence of serum IL-2 but synergy of the factor with IL-2; (3) the factors bind directly to CTLL cells but they do not bind to protein A; and (4) the serum factors are not dialysable but heat labile. The possible pathological implications of the serum factors, particularly for the defective T cell functions in lupus disease, are discussed.

Animals↗

PubMed1996

Fluctuations of antibody to ribosomal P proteins correlate with appearance and remission of nephritis in SLE.

Antibodies to ribosomal P proteins are found in widely variable proportions (up to 42%) of patients with SLE depending on the ethnic background of the patient population. Neuropsychiatric disease was first recognized to have increased prevalence with anti-P and more recently liver and renal disease. We describe four patients with SLE and circumscribed episodes of nephritis of relatively short duration. In two patients, antibodies to ribosomal P protein were the only specificity detected at the time of appearance of active nephritis; and in the other two patients, the appearance and disappearance of anti-ribosomal P was simultaneously found with similar fluctuations in anti-dsDNA titers. Anti-ribosomal P antibodies were measured by Western blot and a P peptide-specific ELISA. These data raise the possibility for a pathogenic role for anti-ribosomal P antibodies in lupus nephritis.

Adult↗

PubMed1996

Variable regions of two murine antibodies that bind the SLE associated 16/6 idiotype.

Experimental systemic lupus erythematosus can be induced in naive mice of different strains using a human monoclonal antibody bearing the 16/6 idiotype and a murine anti-16/6 Id monoclonal antibody designated 1A3-2. Herein we report the isolation of a second anti-16/6 Id antibody, 3F7-8, from BALB/c mice afflicted with experimental SLE. In contrast to the previously reported (1A3-2) anti-16/6 Id monoclonal antibody, mAb 3F7-8 does not induce experimental SLE upon immunization. The variable heavy and light chains of both antibodies were cloned and their sequences were determined. The VH of mAb 1A3-2 was found to express a germ line gene from the Q52 family, with a high homology to an anti-lysozyme antibody. The VH of monoclonal antibody 3F7-8 was found to express a 7183 germ line gene, showing over 95% homology with the VH of 12 anti-Sm antibodies isolated from MRL-lpr mice. Based on sequence homology to other known antibodies, we further demonstrated that monoclonal antibodies 1A3-2 and 3F7-8 bind lysozyme and the Sm ribonucleoproteins, respectively, in addition to their binding to the 16/6 Id.

Amino Acid Sequence↗