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PubMed1986

Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus.

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydroxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metabolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P less than 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.

Adult↗
PubMed1990

Associations between clinical status questionnaire scores and formal education level in persons with systemic lupus erythematosus.

In a study of 124 systemic lupus erythematosus patients, clinical status, according to 5 questionnaire scales, was poorer in patients with less than or equal to 11 years versus those with greater than or equal to 12 years of formal education. These results were statistically significant when adjusted for age, race, sex, and disease duration, though results on some scales were not significant when adjusted for multiple comparisons. These findings further support observations that formal education level is associated with clinical status in rheumatic and other chronic diseases.

Adult↗
PubMed1995

Selection of a gene for apolipoprotein A1 using autoantibodies from a patient with systemic lupus erythematosus.

OBJECTIVE: To investigate immunoreactivity of systemic lupus erythematosus (SLE) sera with apolipoprotein A1, (Apo A1), the major lipid-binding protein of high-density lipoprotein (HDL). METHODS: Since early attempts to identify Apo A1 autoantibodies using standard enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques had been unsuccessful, a mouse complementary DNA lambda phage expression library was screened. RESULTS: A selected clone (MA1) was found to have 82% DNA sequence homology to a segment of human Apo A1. Since there were nonconservative substitutions in the MA1 protein and lack of a complete sequence, it was possible that the SLE patient's antibodies were binding MA1 epitopes that were shared by the complete human protein but had not been conformationally accessible using the earlier techniques. Thus, gamma-irradiated ELISA plates were used as an alternative antigen-binding surface for intact human Apo A1, and high-titer anti-human Apo A1 autoantibodies were then identified in the sera of 5 more SLE patients. CONCLUSION: These findings show that Apo A1 is immunogenic. Apo A1 antibodies may play a role in the decreased HDL levels and Apo A1:Apo B ratios previously reported to occur in subgroups of SLE patients.

Amino Acid Sequence↗
PubMed1998

Psychosocial contributors to mental and physical health in patients with systemic lupus erythematosus.

OBJECTIVE: To delineate psychosocial and systemic lupus erythematosus (SLE)-related medical factors that contribute to the mental and physical health of SLE patients. METHODS: In a cross-sectional study, 44 women completed standardized instruments assessing daily hassles, social support, psychologic distress, and quality of life and underwent a physician examination to assess disease activity and disease damage. Four multiple linear regression analyses were computed to identify factors associated with the following outcomes: patient-perceived psychologic distress and global physical health and physician-assessed disease activity and damage. Variables entered into the regression analyses were: hassles severity, types of social support, SLE disease activity and damage, age, disease duration, education, ethnicity, and global psychologic distress (for the outcomes of self-perceived global physical health and disease activity and damage). RESULTS: The best model explaining global psychologic distress included hassles severity and self-esteem social support. The best model explaining patients' perceptions of their global physical health included hassles severity and tangible social support. Psychologic distress accounted for a significant proportion of variance in both disease activity and damage. CONCLUSION: High stress (assessed by hassles severity), poor social support, and psychologic distress--potentially modifiable variables--are associated with the mental and physical health of SLE patients.

Adult↗
PubMed1996

Upregulation of adhesion molecule expression on endothelial cells by anti-DNA autoantibodies in systemic lupus erythematosus.

The mechanism of vasculopathy in systemic lupus erythematosus (SLE) remains unclear and the evidence for a direct pathogenic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Our study aims to determine whether anti-dsDNA exerts any effect on the expression of adhesion molecules on endothelial cells. IgG was purified from 17 patients with SLE (median anti-dsDNA titer, 404 IU/ml) and from 9 healthy controls (median titer 16 IU/ml). Anti-dsDNA-depleted polyclonal IgG (anti-dsDNA-dep-IgG) (median anti-dsDNA titer 17 IU/ml) was prepared from sera of these patients with SLE by affinity chromatography with DNA cellulose column. Expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVEC) cultured with either control IgG or anti-dsDNA were compared by flow cytometry. The levels of adhesion molecules in the supernatant of cultured HUVEC were assessed by sandwich ELISA. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA expressed a significantly higher mean fluorescence intensity of ICAM-1 and in VCAM-1 and a higher supernatant concentration of ICAM-1 and VCAM-1 but not E-selectin. At the same time, ICAM-1 mRNA was also raised with increased neutrophil adherence in HUVEC incubated with anti-dsDNA. Pretreatment of HUVEC with native DNA or histone before incubation with anti-dsDNA did not increase the expression of adhesion molecules. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenic role in inducing inflammatory injury of vascular endothelium in SLE.

Adult↗
PubMed1998

Prospective randomized trial of two different immunoadsorbers in severe systemic lupus erythematosus.

Experiences with extracorporeal therapy in systemic lupus erythematosus have been published over the last 20 years and more. In addition to plasmapheresis, specific adsorption columns have been developed to deplete pathogenic antibodies and immune complexes in the plasma of patients with SLE. We conducted a prospective randomized trial to compare the efficacy of a disposable adsorption column, which contained a specific ligand, phenylalanine (IMPH-350|Pt, Diamed, Köln, Germany) with a regenerable Ig-adsorbing column containing sheep anti-human antibodies (Ig-Therasorb|Pt, Therasorb, München, Germany). Twenty SLE patients inadequately controlled with corticosteroids, anti-malarials, azathioprine or cyclosporine A, had strong evidence of disease in general, or an organ related SLAM score. They were randomized to receive either a perfusion of IMPH-350, or Ig-Therasorb, immunoadsorbed with 2.5 ml of plasma, three times each. The treatment regime was repeated after 4 weeks when the response was limited or non-existent. Response was defined as a reduction in the SLAM score of at least 30%. SLAM scores in the IMPH group decreased from 14.3+/-5.6 to 9.2+/-6.2 after 1 month and to 9.4+/-3.9 after 6 months; corresponding scores in the Ig-Therasorb group were 18.3+/-5. 5 to 11.2+/-7.6, decreasing to 9.2+/-2.9. After 1 month, 8/10 patients in both groups showed a response; after 6 months, 5/10 patients in the IMPH-350 group and 8/10 in the Ig-Therasorb group fulfilled the response criteria. Reduction of dsDNA antibodies directly after treatment was 50.8+/-6.6% in the IMPH-350 group and 61.0+/-8.0% in the IgTherasorb group. Results indicate that immunoadsorption is an additional option in the treatment of severe SLE. Choice of type of immunoadsorber and immunosuppressive treatment has to take into account the severity and chronicity of common disease activity and organ involvement, as well as economic aspects.

Adult↗
PubMed1988

Presence of interferon and anti-interferon in patients with systemic lupus erythematosus.

Sera from 61 patients with systemic lupus erythematosus (SLE) were serially screened over a period of at least 2 years for IFN and anti-IFN antibodies. IFN concentrations were measured both with a cytopathic effect assay and a more sensitive radioimmunoassay. Of the patients 15% (9/61) had IFN in their serum at one or more occasions as measured in the bioassay (greater than or equal to 6 IU/ml); employing a RIA (greater than or equal to 1 IU/ml) 28% (17/61) of the patients studied were positive for IFN-alpha. Fifteen patients had a measurable interferonemia over 2-16 months; only two patients had detectable IFN in their serum at only one occasion. In five patients, hourly and daily variations of the IFN titer as measured by RIA were found to amount to less than 80%. The IFN activity found in these sera was characterized as IFN-alpha by means of acid stability, cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous and heterologous antisera. IFN antibodies were quantified with a neutralization bioassay, an ELISA, and a radioimmunoassay. Of the 61 patients 5% (3) possessed high titers of anti-IFN antibodies which persisted over 2 years. The IFN-alpha antibody positive patients had an inactive form of the disease over years without visceral involvement but decreased serum complement levels (C4, C3, CH50) and repeated episodes of Quincke-like edema.

Antibodies↗
PubMed1982

Circulating DNA-antibodies in systemic lupus erythematosus.

Sera from 57 patients with systemic lupus erythematosus (SLE) were tested for DNA-antibodies by three different methods: a radioimmunological test using the Farr technique, the Crithidia luciliae immunofluorescence assay for anti-double-stranded (native) DNA (anti-ds-DNA), and a solid-phase immunoenzymatic assay for anti-single-stranded (denatured) DNA (anti-ss-DNA) of IgG and IgM classes. There was a positive correlation between the activity of the disease and the levels of ds-DNA-antibodies and IgG anti-ss-DNA. Patients with active nephritis had a higher amount of anti-ds-DNA and anti-ss-DNA of IgG class than patients with inactive nephritis (P less than 0.05 and 0.01, respectively). Patients with SLE nephritis had lower levels of ss-DNA-antibodies of IgM class than patients without nephritis (P less than 0.02). There was a positive correlation between the IgG-anti-ss-DNA/IgM-anti-ss-DNA ratio and the activity score of the disease. These results suggest that the anti-ss-DNA assay may be useful in the follow-up of SLE. Complement fixing anti-ds-DNA and the highest levels of anti-ds-DNA by Farr assay were usually associated with an active disease, especially nephritis and joint involvement.

Antibodies, Antinuclear↗
PubMed1975

Molecular pathogenesis of systemic lupus erythematosus.

The study of patients with systemic lupus erythematosus revealed the close association of the disease with measles--or a related virus. High titres of antibodies to measles virus were found in patients that correlated with the course of the disease. Immunofluorescence tests revealed measles virus or a related antigen in lupus-affected tissues. Inclusion bodies consisting of paramyxovirus-like ribonucleoprotein structures were regularly detected in both affected tissues and leukocytes. Molecular hybridization of measles virus RNA with DNA from the affected tissues showed that DNA transcripts of measles or a closely related virus are integrated in the cellular nuclear DNA. Possible pathogenetic mechanisms of the disease are discussed.

Adolescent↗
PubMed1992

The presence of antibodies to purified p24gag protein of HTLV-I in sera of patients with systemic lupus erythematosus (SLE).

Sera of patients with systemic lupus erythematosus (SLE) were tested for their reactivity to HTLV-I by western blotting (WB). Seven (18%) of 40 SLE serum samples reacted to the p24gag protein of HTLV-I by WB using purified gag antigens. The specificity of anti-p24gag antibodies in the SLE sera was confirmed by competitive inhibition on WB. Two of the seven patients were shown to be HTLV-I carriers, because HTLV-I infected T cell lines were easily established from their peripheral blood mononuclear cells (PBMC). Except for these two carrier patients, the gag proteins were not detected in the lysates of PBMC by WB using anti-p24gag and anti-p19gag monoclonal antibodies. The gag and pX genes of HTLV-I were not detected by PCR in PBMC of the SLE patients, with the exception of the 2 HTLV-I carrier patients. These results show no direct involvement of HTLV-I in the etiology of SLE. However, the existence of a specific antibody to p24gag in the sera of some of the noncarrier SLE patients suggests a crossreactivity to either unknown viruses or some autoantigens.

Base Sequence↗
PubMed1989

Systemic lupus erythematosus and myelofibrosis.

The coexistence of systemic lupus erythematosus and myelofibrosis is a rare occurrence. A review of the literature available to us revealed only five other patients with this combination. We have recently encountered a patient in whom these two diseases existed concomitantly, and in this report we shall describe the clinical course of our patient and discuss it in comparison with the patients described previously.

Female↗
PubMed1994

Combination therapy for rheumatoid arthritis and drug-induced systemic lupus erythematosus.

Development of drug-induced systemic lupus erythematosus (SLE) is an uncommon complication of the use of D-penicillamine and sulphasalazine. We report two cases of patients with rheumatoid arthritis (RA) who developed symptoms and signs of SLE and suggest that increasing use of these two agents as combination therapy in RA may cause an additive risk to the occurrence of this complication.

Adult↗
PubMed2000

Lower urinary tract symptoms in patients with Sjögren's syndrome and systemic lupus erythematosus.

Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune diseases which have many similarities with interstitial cystitis (IC), a urinary bladder disease with unknown etiology. This survey on the occurrence, severity and nature of lower urinary tract symptoms among patients suffering from SS or SLE showed that these patients have significantly more urinary complaints, especially irritative bladder symptoms, than age- and sex-matched controls. We studied 36 patients with SS, 85 patients with SLE and 121 controls. In these groups, 25%, 29% and 66%, respectively, were free of urinary symptoms. The prevalences of mild symptoms were 61%, 62% and 27%, and severe symptoms 14%, 9% and 7% in the respective groups. SS and SLE patients with urinary complaints reported mostly urinary frequency (27% and 62%) and suprapubic pain (36% and 34%). The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder affections.

Adult↗
PubMed2004

[Psychiatric disorders in rheumatic diseases, as exemplified by systemic lupus erythematosus (SLE)].

Among the rheumatic diseases, systemic lupus erythematosus (SLE) reveals the highest frequency of central nervous symptoms. Psychiatric abnormalities are present in over 90% of the patients, if very mild cognitive impairment is included. The psychiatric syndromes listed by the American College of Rheumatologists encompass cognitive syndromes, including the acute confusional state, anxiety disorders, depressive symptomatology and psychosis. Associations between cognitive impairment and demographic and disease variables, i. e. disease severity, have not been clearly identified so far. The same holds true for the evolution of depressive symptoms. Reactive depression in coping with a chronic disease is, however, a psychologically plausible factor in addition to specific cerebral lesions. Therapeutic interventions in SLE should consist of a combined pharmacological and nonpharmacological treatment. Corticosteroid drugs, however, may be effective in alleviating mild psychiatric symptoms as well.

Adrenal Cortex Hormones↗
PubMed2004

Successful treatment of fulminant pulmonary hemorrhage associated with systemic lupus erythematosus.

We report a patient with systemic lupus erythematosus (SLE) who developed fulminant pulmonary hemorrhage. This patient also showed liver dysfunction, bicytopenia and hyperferritinemia, with an increase in serum levels of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) at the onset of pulmonary symptoms, probably indicating an associated hemophagocytic syndrome. Despite an acute progressive course temporarily requiring mechanical ventilation the patient was successfully treated with continuous drip infusion of tacrolimus, plasmapheresis and intravenous high-dose immunoglobulin and corticosteroid. In this patient increased inflammatory cytokines ascribable to activation of macrophages and/or helper T cells were considered to play an important role in the pathogenesis of the pulmonary hemorrhage. Because this complication is frequently fatal in SLE, intensive therapy, including immunosuppressants and plasmapheresis, should be actively considered as early as possible after onset.

Adrenal Cortex Hormones↗
PubMed1999

A complex case of hepatitis in a patient with systemic lupus erythematosus.

Liver involvement in patients with systemic lupus erythematosus (SLE) is considered rare. Previous treatment with potentially hepatotoxic drugs or viral hepatitis have usually been implicated as the main causes of liver disease in SLE patients. On the other hand, even after careful exclusion of these aetiologies, the problem remains whether to classify the patient as having a primary liver disease with associated autoimmune clinical and laboratory features resembling SLE, such as autoimmune hepatitis, or as having liver disease as a manifestation of SLE. We report the case of an elderly woman who presented with acute hepatitis, who had been diagnosed with SLE 14 years ago and who also had Sjögren's syndrome and anti-phospholipid's syndrome for several years. The histology depicted chronic active hepatitis and, after drug-induced hepatitis and viral hepatitis were excluded, the serological and clinical features were shown to be typical of liver damage caused by SLE. The patient was treated with azathioprine 100 mg/d and prednisone 30 mg/d. The clinical symptoms resolved in 10 days and the laboratory values were normal at the end of the first month of therapy. Prednisone was progressively reduced, during a period of 4 months, to 10 mg/d but azathioprine was kept to the same dose. One year after the diagnoses the patient is still in remission. Although uncommon, hepatic involvement is well recognised in SLE. The interest of this case lies in the differential diagnosis and recognition of this condition, which deserves an aggressive treatment.

Acute Disease↗
PubMed2006

CD19/22 balance relates to improvement of disease activity in systemic lupus erythematosus.

B cells in patients with systemic lupus erythematosus (SLE) are hyperactivated and B-cell receptor signal transduction may be affected by various response regulators. CD19 and CD22 play a major role as regulators of B-cell response. Therefore, we examined CD19 and CD22 expressions on B cells of patients with SLE, and how they were related to disease activity. Thirty-one patients with active SLE were selected and enrolled in this study. Evaluation of CD19 and CD22 expressions on B cells was performed prior to and after treatments with flow cytometry analysis. Disease activity was determined according to the SLE disease activity index score. CD19 and CD22 expressions on B cells in SLE patients revealed no significant differences when compared with the controls. However, improvement of SLE was recognized among patients with an increased ratio of CD22-positive cells. Our results suggest that this balance is a useful marker for determining improvement of SLE disease activity, although the CD19/22 balance does not contribute to the pathogenesis of SLE.

Adolescent↗