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PubMed1975

[Morphologic changes in the chorio-allantoic membrane and organs of chick embryos inoculated with blood of patients with systemic lupus erythematosus (concerning the viral etiology of systemic lupus erythematosus)].

Morphological studies of 14 chorionallantoic membranes and organs of chick embryos which had been infected on the 7--8th day of incubation with leucocytic mass from patients with systemic lupus erythematosus were carried out. Corresponding virological and morphological control studies were performed. The changes observed were repeatedly reproduced in multiple inoculations (from the 2nd to the 16th passage). Apart from morphological changes, which may be listed among general pathological processes (impairment of the circulation, dystrophy, proliferation), changes testifying to a possible cytopathic effect disintegration of nuclei, formation of gigantic cells and multinuclear symplasts were also noted. The most pronounced changes, both in the chorionallantoic membrane and in internal organs, were observed on the 3rd--5th passage and on the 3rd--5th day of incubation following inoculation. They correlated with the clinical activity of the process in patients from whom the blood for inoculation had been taken. The data obtained justify the assumption concerning the existence in the blood of the patients with systemic lupus erythematosus a transplantable agent producing a cytopathic action, and may be considered as a new indirect corroborative evidence in favour of the concept of the viral nature of systemic lupus erythematosus.

Animals↗

PubMed2005

[The diastolic dysfunction of the left ventricle in patients with systemic lupus erythematosus and system scleroderma].

The subjects of the study were 22 patients with systemic lupus erythematosus (SLE) and 18 patients with system scleroderma (SS). The mean age of the subjects was 36.3 +/- 2.4 years, the onset of the disease had taken place 5 to 10 years ago. The control group consisted of 20 practically healthy individuals with no complaints, clinical signs or instrumental data suggesting cardiovascular pathology. In order to evaluate the character of left ventricular (LV) diastolic filling, all the patients underwent transthoracal Doppler analysis with measurement of transmitral flow in four-chamber heart position using apical approach with the control volume at the level of the ends of mitral valvular cusps (computed sonography system ACUSON 128 XP/10). The study found no significant difference between SLE and SS patients in such parameters as LV myocardial mass and LV mass index. All the patients with rheumatic diseases, with or without arterial hypertension (AH), had diastolic dysfunction, which was manifested by increase of atrial systolic contribution into LV filling, prolongation of blood flow slowdown time in the stage of its early filling, and prolongation of LV isometric relaxation time; heart diastolic disorder was accompanied by significant increase of end diastolic pressure in LV cavity. It should be noted that the most prominent changes were found in rheumatic patients with AH, which must be caused by the hypertrophy and remodeling of the myocardium. Myocardial hypertrophy was associated with substantial changes in the ventricular septum, which consisted in its hypokinesia, associated with impairment of myocardial contractility (ejection fraction of 48.3 +/- 3.5%).

Adult↗

PubMed2000

Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.

Adult↗

PubMed2000

Racial group, socioeconomic status, and the development of persistent proteinuria in systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients of Afro-Caribbean and Asian origin living in the United Kingdom have a more severe spectrum of disease compared with the white population but whether this is attributable to genetic host factors or environmental factors is unclear. This study examines time from first symptom to onset of persistent proteinuria, as a marker of renal disease, to assess which factors are important. METHODS: The 189 patients studied were ascertained using multiple methods and included 161 white, 22 Afro-Caribbean and six Asian patients. Time of first observation of persistent proteinuria (>/=0.5 g/day) was taken as onset of renal SLE. Initial univariate analysis to determine which factors are associated with onset of renal disease was followed by using a Cox's proportional hazards regression model enabling analysis of several prognostic factors at the same time. Variables included three measures of socioeconomic status, ethnic group and the presence or absence of different autoantibodies. RESULTS: There was no effect from any socioeconomic variable. Using forwards stepwise selection, the following had independent effects (p<0.05) on the development of renal SLE: Afro-Caribbean race (hazard rate ratio 4.4 (1.9-10.2), compared with white population); and the presence of IgG anti-cardiolipin antibodies (hazard rate ratio 2.6 (1.2-5.7)). CONCLUSION: Differing socioeconomic factors do not explain the increased frequency of lupus nephritis in Afro-Caribbean patients with SLE, but rather there are important genetic or other host differences. The independent effect of IgG anti-cardiolipin antibodies warrants further investigation.

Adolescent↗

PubMed2000

MHC class II-bound self peptides from autoimmune MRL/lpr mice reveal potential T cell epitopes for autoantibody production in murine systemic lupus erythematosus.

The systemic lupus erythematosus-like syndrome in MRL/lpr mice involves high-titered IgG autoantibodies, particularly antinuclear Abs that target histones, DNA, and RNA particles. Although T cell help is required for the generation of antinuclear Abs, the epitopes recognized by such helper T cells are unknown. To address this question, we isolated and sequenced self peptides bound by MHC class II molecules from MRL/lpr mice. We identified a number of peptides that are not seen in similar preparations from nonautoimmune C3H animals. The "abnormal" peptide donors include histone, a protein component of a small nuclear ribonucleoprotein, ribosomal proteins, and RNA processing enzymes. We postulate that the peptides from these donors are T cell epitopes required for the generation of the most frequent antinuclear Abs specificities seen in MRL/lpr mice.

Amino Acid Motifs↗

PubMedDate not supplied

[Anti-nucleic acid antibodies in children with systemic lupus erythematosus and systemic scleroderma and in their relatives living with the probands].

The nature of antibodies to nucleic acids was studied in children of a Caucasian region suffering from systemic lupus erythematosus (SLE) and systemic sclerodermia (SSD). Two types of antibodies (to two- and one-filament DNA) were revealed in SLE, and in SSD mainly--to one-filament DNA. Antibodies to RNA in patients with SLE were specific for two-filament conformation. Immunogenesis disorders of different degree with respect to DNA and RNA were found; this expressed itself in the synthesis of various classes of immunoglobulins to these antibodies (IgG to DNA and IgM to RNA). High incidence of the RNA-binding activity of relatives living together with probands is noted. These data point to a high occurrence of antibodies to denatured DNA and low incidence of the cases of DNA-binding activity in the blood sera of the patients' fathers and brothers. Thus a combination of three factors: viral, genetic and hormonal in the pathogenesis of this disease is possible.

Adolescent↗

PubMedDate not supplied

Systemic lupus erythematosus and systemic scleroderma in patients from the aboriginal people and the newcomers of Yakutia under the extreme conditions of the far north.

There is some information on the course of two main forms of large collagenoses-systemic lupus erythematosus (SLE) and systemic scleroderma (SSD) under the conditions of the North of the Asian part of Russia (Yakutia) in this paper. Seventy-nine cases (59 SLE patients and 20 SSD patients) belonging to different ethnic groups were studied. There were 47 patients of Yakutian nationality, among them SLE 38 patients and SSD nine patients. There were 32 patients (SLE-21, and SSD-11) migrant Europeans. It has been proved that the aboriginal people of the North are more subject to SLE and SSD diseases as compared to the migrants. It has also been proved that the greater spreading of the diseases, with the collagen metabolism disturbance in the first ethnic group, including Marfan's syndrome and rheumatoid arthritis may be explained by genetic peculiarities. Some ethnically stipulated differences in clinical manifestations of two large collagenosis were revealed. Thus, during SLE smaller frequency of the skin impairment in the Yakuts (due to natural hyperpigmentations) is connected with the considerable frequency of large joints impairment and more frequent course of SLE similar to rheumatoid variant with typical wrist deformation. One-third SLE and SSD patients of Yakut nationality reveal "overlap-syndrome", which are typical of other collagenoses, the so-called overlap-syndrome. Some industrial factors (dust of silicon dioxide, vibration, hydrocarbon compounds) are the main reason for the diseases among the newcomers migrants of Russian and Ukranian nationality. One case of silico-lupus was revealed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Antinucleolar autoantibodies demonstrated by monolayers of human fibroblasts in sera from patients with systemic lupus erythematosus, progressive systemic sclerosis and chronic active hepatitis.

Antinucleolar antibody (ANoAb) was tested for in sera from 25 patients with systemic lupus erythematosus (SLE), 61 with progressive systemic sclerosis (PSS), 22 with chronic active hepatitis (CAH) and 28 healthy persons, using immunofluorescence reactivity with acetone-fixed monolayers of cultured human fibroblasts, and a procedure to reveal ANoAb when other antinuclear antibodies were concurrently present. ANoAb was found on direct testing in sera from 6 patients with SLE, 15 with PSS and 7 with CAH, but not in any of 28 sera from healthy persons; homogeneously reactive antinuclear antibody was also present in the serum of these 6 cases of SLE, in 6 of the 15 with PSS and in 3 of the 7 with CAH and, in SLE specifically, pre-treatment of fibroblast monolayers with DNase "unmasked" the presence of ANoAb in a further 7 sera which had shown only homogeneous nuclear staining in fibroblasts. ANoAb belonged to the IgG, IgM and IgA class in sera from cases of SLE and PSS, and to only the IgG and IgM class in sera from cases of CAH. ANoAb titres were highest in patients with PSS. ANoAb were sensitive to RNase in 5 cases, to RNase and DNase in 6, and were sensitive to combinations of RNase, DNase, NaC1, and trypsin in the remaining cases. We conclude that (i) fibroblast monolayers are a suitable substrate for the demonstration of ANoAb, (ii) homogeneous staining of cell nuclei may mask ANoAb, so that the incidence of ANoAb becomes higher in SLE than in PSS, (iii) low-titre ANoAb in CAH not visualized in frozen tissue sections may be detected on fibroblast monolayers, and (iv) nucleolar antigens probably include RNA, RNA bound to DNA, and RNA bound to proteins.

Autoantibodies↗

PubMed2003

Usefulness of technetium-99m sestamibi myocardial perfusion SPECT in detection of cardiovascular involvement in patients with systemic lupus erythematosus or systemic sclerosis.

The main purpose of the study was to evaluate the utility of technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (Tc-99m sestamibi SPECT) in detection of cardiac involvement in systemic lupus erythematosus (SLE) or systemic sclerosis (SS) patients. Fifty SLE or SS female patients with cardiac symptom/sign such as chest discomfort and/or dyspnea and/or occasionally palpitation and 50 SLE or SS female patients without any cardiac symptom/sign were investigated using Tc-99m sestamibi SPECT during rest and stress after dipyridamole infusion. Twenty-five age- and sex-matched healthy females were also included as controls in this study. The results of Tc-99m sestamibi SPECT were classified into four types including normal, persistent perfusion defect (PD), reversible perfusion defect (RD), and reverse perfusion defect (RR). The results of Tc-99m sestamibi SPECT in the 25 healthy females were normal. Perfusion abnormalities were detected in 44/50 (88%) symptomatic SLE or SS patients. However, myocardial perfusion abnormalities were only detected in 19/50 (38%) asymptomatic SLE or SS patients (P value<0.05 by a chi2 test). However, for risk factor of coronary artery disease and abnormal resting EKG, the incidences were not significant between symptomatic and asymptomatic patients (P values >0.05 by a chi2 test). Tc-99m sestamibi SPECT is a useful noninvasive imaging modality to detect cardiac involvement in symptomatic or asymptomatic SLE or SS patients.

Adult↗

PubMed2003

Von Willebrand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue diseases (systemic lupus erythematosus and systemic sclerosis).

BACKGROUND AND OBJECTIVES: Autoantibodies inactivating the von Willebrand factor (VWF) cleaving protease, ADAMTS-13, are among the most frequent causes of thrombotic thrombocytopenic purpura (TTP). We evaluated whether or not ADAMTS-13 deficiency and autoantibodies inactivating the protease prevalent in patients with the prototypic autoimmune diseases systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). DESIGN AND METHODS: We measured, in parallel, the protease and VWF antigen (VWF:Ag) in 123 patients, 36 of whom had SLE and 87 of whom had SSc. In 14 patients with either disease who had low plasma protease levels (below 40%) we also looked for anti-ADAMTS-13 inactivating antibodies. RESULTS: ADAMTS-13 levels were significantly lower in SLE (p=0.0013) and in SSc (p=0.0002) than in normal controls. No anti-ADAMTS activity was measurable in patients with low ADAMTS-13 levels. VWF:Ag was high in both SLE and SSc (p=0.001). INTERPRETATION AND CONCLUSIONS: Systemic connective tissue diseases are other conditions besides TTP that are associated in some instances with low but detectable levels of ADAMTS-13. Autoantibodies inactivating protease activity are not the cause of the low plasma levels of ADAMTS-13.

ADAM Proteins↗

PubMedDate not supplied

Echographic diagnosis of cardiac involvement in systemic lupus erythematosus and systemic scleroderma.

The great frequency and severity of cardiac involvement in collagen diseases have proved to be an important diagnostic, prognostic and therapeutic problem. In the last few years the value of echographic examination in the estimation of the pathologic cardiac changes in the course of systemic lupus erythematosus (SLE) and of systemic scleroderma (SS) has considerably increased making the object of numerous studies. In this paper the results obtained in some of these studies are estimated comparatively.

Cardiomyopathies↗

PubMedDate not supplied

Myocardial involvement in systemic lupus erythematosus and systemic sclerosis--pulsed Doppler echocardiographic evaluation of left ventricular diastolic function.

Myocardial involvement (MI) in connective tissue diseases is commonly found at autopsy but seldom recognized clinically. To assess the subclinical MI, the left ventricular (LV) diastolic function was studied in 16 patients with systemic lupus erythematosus (SLE) and 15 patients with systemic sclerosis (SSc) by means of pulsed Doppler echocardiography. Patients with abnormal LV systolic function were not included. A control group (C) included 16 sex and age-matched healthy subjects. The parameters analyzed were: peak early diastolic flow velocity (E), peak late diastolic flow velocity (A), E/A ratio, isovolumic relaxation time (IRT). LV diastolic function was found impaired in SLE and SSc patients even when systolic function was normal as could be demonstrated by pulsed Doppler echocardiography.

Cardiomyopathies↗

PubMed1993

Serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and systemic idiopathic vasculitis.

Soluble interleukin 2 receptor (sIL2R) may be used as an index of immune perturbation. We report on the correlation between the serum levels of sIL2R, as assessed with a sandwich-ELISA, and disease activity in 61 patients with Systemic Lupus Erythematosus (SLE) and in 15 with systemic idiopathic vasculitis (SIV). The mean levels of sIL2R in SLE and SIV patients were significantly higher than in healthy controls and higher values were detected in patients with active disease or severe organ involvement or infection. We also studied patients with clinically silent SLE, characterized by the presence of several immunologic abnormalities. The sIL2R mean level in this group did not differ from that of quiescent SLE patients, suggesting that immunologic alterations are present even in inactive SLE. Finally, the sIL2R assay showed higher sensitivity and specificity than most of the common immunologic parameters.

Adolescent↗

PubMed1999

IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner.

OBJECTIVE: To investigate the ability of anti-endothelial cell antibodies (AECA) to modulate endothelial cell function. METHODS: The effects of purified IgG from 11 patients with systemic lupus erythematosus (SLE) and 4 patients with systemic vasculitis on the expression of adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin) by human umbilical vein endothelial cells and on the adhesion of the human promyelocytic cell line U937 were examined in vitro. RESULTS: IgG from 6 of 8 AECA-positive SLE patients and 3 of 3 AECA-positive systemic vasculitis patients up-regulated adhesion molecule expression and leukocyte adhesion to endothelial cells. The 4 AECA-negative samples had no effect. Transfer experiments demonstrated that at later time points (2-8 hours) after AECA addition, endothelium-derived interleukin-1 (IL-1) accounted for the ability of AECA to increase leukocyte adhesion. However, even within very short times after addition of AECA (<30 minutes), endothelial cells released a distinct transferable mediator with similar effects. CONCLUSION: AECA in patients with SLE or systemic vasculitis may contribute to pathogenesis by increasing leukocyte adhesion to endothelial cells. AECA act by inducing the release of at least two endothelium-derived mediators, one (as-yet-unidentified) rapidly and another (IL-1) more slowly, both of which stimulate endothelial cells in an autocrine manner.

Antibodies, Blocking↗

PubMed1997

[Cardiovascular and pupillary autonomic and somatosensory neuropathy in chronic diseases with autoimmune phenomena. A comparative study of patients with Crohn disease, ulcerative colitis, systemic lupus erythematosus, progressive systemic sclerosis and type I diabetes mellitus].

BACKGROUND: During the last years, examination of autonomic nervous function and of autonomic neuropathy has attracted attention not only in diabetes mellitus research but also in other areas of internal medicine. However, patients with various chronic diseases with autoimmune phenomenons have never been investigated in a comparative study with standardized examination techniques. Hence, the aim of the study was to examine the prevalence and the severity of autonomic neuropathy in patients with the following chronic diseases. PATIENTS AND METHODS: We investigated 28 patients with Crohn's disease (CD: age: 32.4 +/- 2.0 y), 17 patients with ulcerative colitis (UC: 39.7 +/- 3.6 y), 39 patients with systemic lupus erythematosus (SLE: 34.9 +/- 2.0 y), 38 patients with progressive systemic sclerosis (pSS; 51.5 +/- 2.4 y) and 65 patients with insulin-dependent diabetes mellitus (IDDM: 35.5 +/- 1.6 y). Cardiovascular autonomic (cANP), pupillary autonomic (pANP), and sensorimotor (ssNP) neuropathy were assessed by standardized techniques. RESULTS: Prevalence rates for cANP, pANP and ssNP were found to be 0%, 19%, and 7% in CD, 6%, 25%, and 18% in UC, 5%, 29%, and 10% in SLE, 11%, 16%, and 32% in pSS, and 26%, 66%, and 29% in IDDM, respectively. CONCLUSION: The study demonstrated patients with IDDM to have the highest prevalence rates of cANP and pANP. Patients with other chronic diseases, particularly SLE, pSS and UC, had high prevalence rates of pANP. This may be due to alterations of structures of the central nervous system in these patients. cANP was rare in patients with inflammatory bowel disease and ssNP was found very often in patients with pSS, probably due to local fibrotic lesions. The various disease groups differ in the pattern and severity of autonomic and sensorimotor neuropathy, which indicates that different structures and neuropathogenic mechanisms may be involved.

Adult↗

PubMedDate not supplied

The pathophysiology of lupus erythematosus.

Systemic lupus erythematosus disseminatus in addition to the more restricted, lupus-like syndromes, is the consequence of an attack by the immune system on the cellular and nuclear structures of the body. These disorders are also frequently associated with disturbances of the coagulation cascade. In this review paper, the factors that provoke or enhance these disturbances are considered, as well as the way by which this provocative effect is exerted. An intermutual relation between various elements is described, whereby congenital factors (heredity, race) and non-congenital factors (sex hormones, pregnancy, environment, ultraviolet light, drugs, infection) play a role. These factors induce the activation cascade of the disease, via two different axes: on the one hand modifications in the DNA structure, on the other immune stimulation. This eventually results in tissue damage.

Causality↗

PubMedDate not supplied

Gender impact in systemic lupus erythematosus.

OBJECTIVE: Systemic Lupus Erythematousus (SLE), an autoimmune disease of unknown etiology manifesting as a pleomorphic systemic disease, affects mostly females, (female:male ratio 9:1). Clinical differences between genders, including a higher death rate in males, has been reported. Here we compared clinical manifestations and the 5-year survival probability in Mexican male and female crossbred cases living under similar socioeconomic conditions. A systematic review of published literature was also carried out. MATERIAL AND METHODS: SLE patients treated at the Instituto Nacional de Cardiología "Ignacio Chávez" México City who fulfilled at least four classification criteria (ACR) were included. The frequency of clinical variables with emphasis on cardiovascular findings before and after the diagnosis were described, disease activity based on a validated scale (SLEDAI) was determined, and the 5-year survival rate was estimated. RESULTS: There were 33 men and 158 women, average age of 31 in both groups ranging from 7 to 65 and from 10 to 75 year in male and female patients respectively; both groups were followed for 3.8 years (median), average activity was of 12 points with a range of 5 to 23 in men, and 11 with a range of 2 to 24 in women. Main clinical characteristics in men were: discoid lupus, psychosis, pericarditis, lymphopenia, thrombocytopenia and SLE kidney disease. Immunological tests showed gender-linked differences in regard auto-antibodies (U1-nRNP, Sm, anticardiolipine and false VDRL) and hypocomplementemia. Cardiovascular features and survival rate were not different between gender. CONCLUSION: Male Mexican SLE patients share clinical findings with other male SLE cases reported everywhere as can be deducted from systematic literature review covering 25-year.

Female↗

PubMed1980

Discoid lupus erythematosus and tuberculosis simulating systemic lupus erythematosus.

A patient with chronic discoid lupus erythematosus was admitted with fever, arthralia, pleuropericarditis, and a history of leukopenia. He was initially believed to have systemic lupus erythematosus (SLE), but extensive evaluation showed negative immunologic studies and the presence of acid-fast organisms on pericardial biopsy specimens with cultures positive for Mycobacterium tuberculosis. Discoid lupus erythematosus patients with extracutaneous manifestations should be carefully studied for concurrent illness, especially when serologic evidence fo SLE is negative.

Adrenal Cortex Hormones↗