Early aspects of the intrarenal distribution of mercury after the intravenous administration of mercuric chloride

It is generally considered that the clinical manifestations of human and canine systemic lupus erythematosus (SLE) are similar in many respects. However, there are differences in serological markers of SLE between the two species, which has led to much discussion on which immunopathological criteria might be appropriate in the diagnosis of the canine disorder. Further studies on canine SLE will need to address these issues, so that definitive diagnostic indices may be employed. Areas which require to be re-assessed, in particular, include the applicability of assays for antibodies to double-stranded DNA--a hallmark of human SLE, a re-evaluation of the anaemia associated with canine SLE and an index of the clinical activity of the disease process.     

The elevation of plasma DNA in patients with systemic lupus erythematosus is attributable to increased DNA release and defective DNA binding of mononuclear cells

BACKGROUND: Although immunoprecipitable DNA has been found in a subgroup of patients with systemic lupus erythematosus (SLE) exhibiting systemic vasculitis and/or central nervous system involvement, the mechanism for elevated plasma DNA in these patients is poorly understood. METHODS: The plasma DNA concentrations and reactivity of serum and lymphocytes to six species of double-stranded DNA from calf thymus, human placenta, Escherichia coli, Micrococcus lysodeikticus, Clostridium perfringens and poly (dG.dC). poly (dG.dC) were measured in twenty-seven patients with active SLE. To understand the mechanism of increased plasma DNA in SLE, the DNA binding and release of the mononuclear cells were examined. RESULTS: Compared with the controls, the incidence of the presence of plasma DNA was markedly increased in SLE (59.3% in SLE vs. 7.4% in controls) as detected by counterimmunoelectrophoresis. Except for DNA from Clostridium perfringens, the reactivity of lupus sera to various DNA samples was significantly higher than that of the controls. The reactivity of lymphocytes to 6 species of DNA (as defined by 3H-thymidine incorporation of the cells) was also higher in SLE patients. In DNA binding and releasing experiments, patients with SLE were found to have decreased 3H-DNA binding activity (0.169 +/- 0.018 micrograms/2 x 10(6) cells in SLE vs. 0.283 +/- 0.02 micrograms/2 x 10(6) cells in controls, p = 0.001) but to have increased spontaneous release of DNA (1,465 +/- 412 cpm in SLE vs. 630 +/- 179 cpm in controls, p = 0.0173) in mononuclear cells. CONCLUSIONS: The results suggest that some subsets of lymphocytes can be sensitized by different DNA samples in vivo to increase endogenous DNA release from mononuclear cells, which in addition to decreased DNA clearance as has been previously reported, may be responsible for the elevation of plasma DNA in patients with SLE.     

Highly cationic anti-DNA antibodies in patients with lupus nephritis analyzed by two-dimensional electrophoresis and immunoblotting

The relationship between chemical properties of anti-DNA antibodies (Abs) and lupus nephritis was investigated. The anti-DNA Abs in sera from systemic lupus erythematosus (SLE) patients were separated by two-dimensional electrophoresis (2-DE) and immunoblotting with goat anti-human IgG Abs. Highly cationic anti-DNA Abs were detected in deoxyribonuclease I (DNase I)-treated sera from patients with lupus nephritis (in 8 of 9 cases) but not in the sera from SLE patients without nephritis (in 0 of 9 cases), normal subjects, or patients with other renal diseases (in 0 of 7 cases). The mean titers of anti-dsDNA Abs in patients with lupus nephritis were not significantly different from those in SLE patients without nephritis. The highly cationic anti-DNA Abs in the sera disappeared after incubation with heparin-Sepharose. These results suggest that highly cationic anti-DNA Abs are specific for lupus nephritis and may be involved in development of lupus nephritis via the binding to glycosaminoglycans on the endothelial cell surface.     

Stroke and meningitis in a case of SLE with anti-phospholipid antibodies

Anti-phospholipid antibodies (aPL) are concerned with many central nervous system diseases in systemic lupus erythematosus (SLE). However, no report has described the relationship between aseptic meningitis and aPL in SLE. We report a case of SLE with aPL, presenting cerebral infarction and aseptic meningitis. A 14 year old female with SLE with aPL experienced cerebral infarction and recurrent aseptic meningitis. Combination therapy with steroids and aspirin improved the condition and prevented relapses. The aPL are associated with cerebral infarction, even in young patients with SLE. In addition, aPL may induce aseptic meningitis in SLE.     

Efficacy of immunosorption in patients with systemic lupus erythematosus: double blind controlled trial

Efficacy of immunosorption (IS) employing perfusion of whole blood through activated charcoal containing DNA was studied in 11 patients with systemic lupus erythematosus (SLE). 11 SLE patients exposed to hemosorption on charcoal free from DNA served as controls. When used in combination with intensive therapy (corticosteroids and cytostatic immunosuppressant), IS produced a positive effect on lupus nephritis symptoms in 8 out of 10 patients with kidney affection. AntiDNA antibodies blood level decreased by 53.6% after two IS procedures, while only by 36.4% after nonselective hemosorption. Reduced count and functional activity of B-cells recorded after IS contribute much to final outcome of the treatment.     

Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus

OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.     

In vitro spontaneous and UVB-induced lymphocyte apoptosis are not specific to SLE

We studied in vitro spontaneous and ultraviolet light (UV)-induced lymphocyte apoptosis in patients with systemic lupus erythematosus (SLE, n = 11), cutaneous lupus erythematosus (CLE, n = 8), and other collagen diseases (n = 6), as well as normal individuals (n = 6). Apoptosis was confirmed by the presence of a 180 bp DNA ladder on gel electrophoresis. UVB-induced apoptosis was observed in 4 of 11 patients with SLE (36.3%), 3 of 8 patients with CLE (37.5%) and 2 of 6 patients (33.3%) with other collagen diseases. There was no clinical correlation between clinical photosensitivity and UV-induced apoptosis. Similarly, spontaneous apoptosis was also found in lymphocytes from patients with diseases other than SLE. No apoptosis was found in normal subjects with or without UVB irradiation (25 mJ/cm2). These data suggest that UV-induced lymphocyte apoptosis may not be specific to SLE but may be common in collagen diseases.     

Lipoprotein profile, diet and body composition in athletes practicing mixed an anaerobic activities

To investigate the prevalence and possible role of anti-endothelial cell antibodies (AECA) in the pathogenesis of systemic lupus erythematosus (SLE), cell membrane antigen was prepared from cultured human umbilical vein endothelial cells and immunoblotting performed to detect AECA in SLE sera. IgG-AECA could be detected in 41 (86%) of 47 SLE patients. They were highly specific and failed to react with membrane antigens of human peripheral blood mononuclear cells or granulocytes. IgG-AECA reacted with endothelial membrane antigens which ranged from 15 to 200 kDa in molecular size. Further analysis of the antigens reacting with IgG-AECA revealed some interesting correlations between specific species of antibodies with certain clinical manifestations. Thus, patients having lupus nephritis, vasculitis, and hypocomplementemia had IgG-AECA against a 66-kDa membrane antigen; those with thrombocytopenia had IgG-AECA against a 55-kDa antigen; those with pleuritis had IgG-AECA against an 18-kDa antigen. These results indicate that IgG-AECA in the sera of SLE patients consist of heterogenous species.     

Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus

OBJECTIVE: To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). METHODS: We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta2-glycoprotein I (anti-beta2-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay. RESULTS: There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta2-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p=0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS. CONCLUSION: Our data suggest that increased levels of IgG anti-beta2-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.     

Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia

The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed against the major platelet membrane glycoproteins (GP IIb-IIIa, GP Ib-IX, GP Ia-IIa and GP IV) in patients where SLE and APAS were associated or not with thrombocytopenia. Results were compared with a series of 26 ITP patients, 46% of whom were shown to possess anti-platelet antibodies directed against one or more of the platelet surface glycoproteins. When APAS was associated with thrombocytopenia, 7/10 patients possessed antibodies against GP IIb-IIIa and/or GP Ib-IX. For SLE patients with thrombocytopenia, 6/10 patients were shown to have antiplatelet antibodies against GP IIb-IIIa, GP Ib-IX or GP IV. In contrast, for APAS (n=11) and SLE patients (n=11) without thrombocytopenia, only one patient had an antibody directed against GP IIb-IIIa and one patient had an antibody to GP IV. Our results suggest that antibodies directed against major platelet membrane glycoproteins may play a role in the thrombocytopenia that is seen during SLE and APAS.     

Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein

The prevalence and clinical significance of antibodies against beta2-glycoprotein I (anti-beta2GPI) and antibodies against oxidized low-density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti-beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.     

pH-sensitive liposomes for receptor-mediated delivery to chicken hepatoma (LMH) cells

The purpose of this study was to evaluate pediatric patients with systemic lupus erythematosus (SLE) to determine 1) the incidence of thrombosis, 2) the incidence of antiphospholipid antibodies, and 3) whether there is an association between the presence of antiphospholipid antibodies and thrombosis. We performed a cross-sectional cohort study in 59 consecutive SLE patients who had been managed at rheumatology clinics in two pediatric hospitals. A history, questionnaire, and chart review were completed by the study nurse blinded to laboratory results. Only the thrombotic events that could be substantiated by review of radiographic tests were accepted. The presence of antiphospholipid antibodies was determined by prospective analysis for a lupus anticoagulant and anticardiolipin antibodies on two separate occasions at least 3 mo apart. Patients were considered to be positive if one or more tests were positive on both occasions. Thirteen thrombotic events occurred in 10 of the 59 patients (17%). Fourteen patients (24%) were classified as positive for lupus anticoagulant, and 19 patients (27%) were classified as positive for anticardiolipin antibodies. A significant relationship between the presence of a lupus anticoagulant and a thrombotic event was shown: odds ratio 28.7 (95% confidence interval 4.03-138.2, p < 0.001). A nonsignificant trend was seen for the presence of an anticardiolipin antibody and a thrombotic event: odds ratio 2.12 (95% confidence interval 0.71-22.8, p=0.08). We conclude that in pediatric patients with SLE: 1) a significant proportion of patients have thrombotic events, 2) a significant proportion of patients have antiphospholipid antibodies, and 3) there is a significant relationship between the presence of a lupus anticoagulant and thrombotic events.     

Antibodies binding to anionic phospholipids but not to oxidized low-density lipoprotein are associated with thrombosis in patients with systemic lupus erythematosus

OBJECTIVE: Elevated levels of antibodies against oxidized low-density lipoprotein (LDL) frequently occur in patients with systemic lupus erythematosus (SLE) and these antibodies crossreact in many sera with anticardiolipin antibodies, known to be associated with thrombosis. Therefore, a study was carried out to assess the mutual relationship between antibodies against oxidized LDL and thrombosis. METHODS: The occurrence of IgG class antibodies against oxidized LDL, cardiolipin and phosphatidyl serine were determined by enzyme-linked immunosorbent assay in a series of 146 patients with SLE. Twenty-one patients had had thromboembolic complications. At least one of three tests used to detect lupus anticoagulant was positive in 34 out of 133 patients. RESULTS: The level of antibodies against oxidized LDL correlated significantly with that of antibodies against cardiolipin (r = 0.52) but only marginally with antibodies against phosphatidyl serine (r = 0.18). Antibodies against cardiolipin and phosphatidyl serine, but not those against oxidized LDL, were significantly associated with the presence of lupus anticoagulant (odds ratios of the risk in the highest tertile relative to the lower tertiles of the antibody were 5.3, 6.9 and 1.1, respectively) and with thrombosis (odds ratios 2.5, 4.0 and 1.0, respectively). CONCLUSION: The observations suggest that only those antibodies reacting specifically with cardiolipin and phosphatidyl serine are associated with thrombosis and with the presence of lupus anticoagulant in patients with SLE, whereas antibodies crossreacting with oxidized LDL and those reacting specifically with oxidized LDL are not associated.     

N-3 and n-6 fatty acid metabolism in undifferentiated and differentiated human intestine cell line (Caco-2)

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. Central nervous system involvement in SLE is multifactorial, thrombotic events, antineuronal antibodies, hypertension, infection, side effects of drugs etc. Antiphospholipid antibodies may play a role in focal neurological manifestations in SLE. In the absence of SLE, different neurological symptoms are well associated with antiphospholipid antibodies including stroke, seizures, dementia, migraine, ocular ischemia, chorea, transverse myelopathy, cerebral phlebitis. Other association are more controversal like Guillain Barré syndrome, motor neuron disease, communicating hydrocephalus. In all patients with antiphospholipid antibodies with neurological involvement, cerebral MRI may be performed with an echocardiographic study because a possible association with Libman and Sacks endocarditis, valve dysfunction or cardiac thrombus source of cerebral ischemia.     

Altered platelet magnesium and plasma and urinary soluble form of intercellular adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes mellitus (IDDM) patients with microalbuminuria

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we investigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.     

Clinical features and evolution of antinuclear antibody positive individuals in a rheumatology outpatient clinic

OBJECTIVE: To identify individuals with antinuclear antibodies (ANA) not fulfilling criteria for systemic lupus erythematosus (SLE) or other connective tissue diseases (CTD); to describe their clinical and serological features, to identify factors indicating evolution to SLE. METHODS: A case-control study, based on retrospective evaluation of clinical files. The cases were ANA positive individuals (n = 50) examined in a medical outpatient setting, for symptoms compatible with SLE, but not fulfilling SLE classification criteria. Two patients with SLE were matched to each case in terms of age at initial symptom onset and sex. Thyroid autoimmunity was assessed by detecting antithyroid antibodies. Fisher's exact test and conditional logistic regression were used to evaluate the predictive ability of initial findings for SLE development. RESULTS: ANA positive individuals suspected of having a CTD present a wide variety of symptoms and findings, usually at the 4th to 5th decade of life. Antibodies to Sm and U1RNP were absent; anti-Ro(SSA) and anti-La(SSB) occurred in 6%, while anti-dsDNA occurred in less than 10% of the cases. Arthritis, butterfly and discoid rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies are the initial findings indicating evolution to SLE. Hematological abnormalities such as leukopenia and thrombocytopenia as well as constitutional symptoms such as easy fatigue and arthralgias are not associated with evolution to SLE. Antithyroid antibodies were detected in 16% of the cases and 2.3% of controls. CONCLUSION: ANA may connote a form of systemic autoimmunity that is expressed as a wide variety of complaints, even in the absence of a definite diagnosis of CTD. Arthritis, rash, Raynaud's phenomenon, and anti-Ro/SSA antibodies indicate evolution to SLE. Autoimmune thyroid disease occurs in ANA positive individuals not fulfilling SLE classification criteria rather than in patients with SLE.     

Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is recognized as a variant of Systemic lupus erythematosus (SLE) and affects mainly middle-aged Caucasian women. The clinical picture is characterized by typical skin lesions, joint or muscle pain and occasionally arthritis. Serious systemic manifestations such as affection of the central nervous system and kidneys are rarely observed. Most SCLE patients are strongly photosensitive, which is associated with the presence of anti-SSA and/or anti-SSB antibodies. The disease can mimic both Sj?gren's syndrome and SLE. The course is characterized by exacerbations and remissions. SCLE sometimes occurs concomitantly with other diseases of both a rheumatological or non-rheumatological nature, and it has also been discussed whether SCLE might be an example of a paraneoplastic syndrome. Treatment with hydroxychloroquine is usually effective. Five patients with SCLE are described.     

Anti-DNA, anti-deoxyribonucleoprotein and rheumatoid factor measured by ELISA in patients with systemic lupus erythematosus, Sj?gren's syndrome and rheumatoid arthritis

Serum concentrations of anti-DNA and anti-deoxyribonucleoprotein (NP) antibodies were measured in parallel by standardized ELISA methods with a polyvalent anti-immunoglobulin conjugate in patients with systemic lupus erythematosus (SLE), Sj?gren's syndrome (SS) and rheumatoid arthritis (RA). High levels of these antibodies predominated in systemic lupus erythematosus. While an appreciable incidence of antibodies also occurred in SS and RA, they were mostly at lower levels. By using heavy chain-specific anti-immunoglobulin conjugates, IgG antibodies to both DNA and NP were found in SLE more frequently and at higher levels than were IgM antibodies. In contrast, IgM antibodies to DNA and NP predominated in SS and RA. The immunoglobulin class of the anti-DNA and anti-NP responses in a given SLE patient were not infrequently different. For example, a patient might show a very high IgG but low IgM anti-DNA value, with the reverse being true for anti-NP. IgG anti-DNA antibodies were significantly associated with depressions of C3. During changes in SLE serology, normalization of DNA binding by Farr radioimmunoassay and/or complement was most frequently associated with normalization of the IgG anti-DNA antibody concentrations. In patients simultaneously possessing elevated levels of anti-DNA, anti-NP and rheumatoid factor (RF), absorption with aggregated human IgG usually decreased only the RF activity. In some, however, such absorption decreased all three antibody values simultaneously. The latter findings support observations that some RF possess antinuclear properties.     

Evidence of autoantibodies to cell membrane associated DNA (cultured lymphocytes): a new specific marker for rapid identification of systemic lupus erythematosus

OBJECTIVE: Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA. METHODS: Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes. RESULTS: This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sj?gren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible. CONCLUSION: This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.