Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All patients with systemic lupus erythematosus in a prospective, epidemiologically based study within a defined area in southern Sweden were invited to participate in an investigation of cardiac function. From 1981 to 1988, 101 patients were included in the study, and 75 of them were investigated according to a fixed protocol by echocardiography, Doppler cardiography, electrocardiography (ECG) at rest and at exercise, and myocardial scintigraphy (in patients whose ECG became abnormal during exercise). IgG anticardiolipin antibodies (IgG aCL) were determined by ELISA. Twenty of the 75 patients (27%) had valvular disease and 12 of these (60%) had increased concentrations of IgG aCL, compared with 12 of 55 (22%) without valvular disease (p less than 0.01). Pericardial effusion was detected in 14 patients (19%) during the study period. Mild pulmonary hypertension was found in 11 patients (16%), who also had increased frequency of IgG aCL. Myocardial infarction had occurred in 7 patients, 3 of whom were women less than 40 years of age. Echocardiography revealed regional hypokinesis or akinesis in 5 of the patients with myocardial infarction. Exercise testing revealed low work capacity in 13 of 54 patients (24%), the limiting symptoms being mainly exhaustion or musculoskeletal pain. An abnormal resting ECG was found in 9 of the patients participating in the exercise test. During exercise, abnormal ST-depression was observed in 8 patients, 2 of whom developed angina. Myocardial scintigraphy was performed in 6 of these patients, revealing reversible uptake defects in all. Prolonged glucocorticoid treatment was associated with valvular abnormalities as well as myocardial infarction. Valvular abnormalities and IgG aCL appeared to be risk factors for cerebral infarction.
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PMID:Cardiovascular disease in systemic lupus erythematosus. A study of 75 patients form a defined population. 151 95

The functional effects directly induced by dialysis membranes on peripheral monocytes were analyzed in a plasma-free model of simulated dialysis using Cuprophan, cuprammonium rayon, polyacrylonitrile, polymethylmetacrilate and polysulphone membranes. A severe reduction of monocyte phagocytosis of IgG-coated erythrocytes was found by using Cuprophan and cuproammonium rayon. The cytofluorimetric analysis of several cell surface receptors, involved in the immune phagocytosis and recognizable by five quoted monoclonal antibodies, did not reveal any significant change. The defective phagocytosis of the IgG-coated erythrocytes by monocytes, due to the exposure to cellulose-derived membranes, was paralleled by an impaired interiorization of heat-aggregated human immunoglobulins, as analyzed by electron microscopy. The cell membrane binding of aggregated immunoglobulins was found to be unaffected. The defect was associated to a remarkably depressed generation of reactive oxygen species after Zymosan stimulation. Therefore, the defective immune phagocytosis induced by exposure of monocytes to cellulosic membranes was not due to a receptor rearrangement or an impaired binding of ingestible particles, but to a reduced internalization capacity probably related to an energy source exhaustion (as shown by the lack of response to stimuli able to induce oxidizing species production). These features are similar to those described in monocytes from acute systemic lupus erythematosus patients.
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PMID:Functional changes of monocytes due to dialysis membranes. 270 68

Interleukin 2 (IL 2) secretion in response to mitogenic stimulation in vitro is strongly reduced in circulating T lymphocytes from patients with SLE. It is still not clear how this abnormality relates to the B cell hyperactivity in the disease. Some investigators proposed that an intrinsic T helper cell defect could lead to suppressor cell dysfunction and autoimmunity. Others have found that in fact increased suppressor cell activity can cause IL 2 hyposecretion. In the present study we report that the IL 2 secretion in response to PHA plus PMA by T cells from patients with SLE, which initially was decreased by a factor of 10 as compared with the IL 2 secretion in blood donor T cells, was restored when the T cells were rested for 2 to 3 days in culture before stimulation. IL 2 hyposecretion in SLE T cells and the kinetics of normalization in culture were not changed by the addition of normal adherent cells during the stimulation with PHA/PMA, occurred in the absence of significant cell death or proliferation or change of the T4:T8 cell ratio during the resting culture, were not due to a maturation of immature T6-positive cells (less than 1.5% T6 cells in SLE T cells), and also occurred in T8-depleted T4 cells alone. Furthermore, a normalization of IL 2 secretion took place in the presence of either SLE serum or normal serum, and the addition of fresh autologous T cells to 3-day-cultured SLE T cells did not cause suppression of IL 2 secretion. These data show that some rapidly reversible defect occurs in circulating T helper cells in SLE. That this could reflect an exhaustion of T helper cells that have been activated in vivo is discussed.
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PMID:The interleukin 2 secretion defect in vitro in systemic lupus erythematosus is reversible in rested cultured T cells. 294 62

In autoimmune diseases striking abnormalities of T and B cell activation and of cytokine production are present. In 14 patients with autoimmune hemolytic anemia (AIHA), idiopathic or in the course of: lymphoma, B hepatitis, carcinoma, drug therapy (alpha-methyldopa), systemic lupus erythematosus (SLE), and not yet submitted to immunosuppressive therapy, the PBL proliferative response to PHA and the IL1 alpha, IL2, IL4 and IL2R serum levels have been valued. While the stimulation index of PBL was strongly reduced in 10 cases (64 +/- 56 vs 138 +/- 45 in the control group), IL1 alpha, IL2 and IL2R were greatly increased in all the patients, and IL4 in 5 (IL1 alpha :199 +/- 268 pg/ml in patients vs 0.30 +/- 0.2 in controls; IL2:716 +/- 311 pg/ml vs 16 +/- 4; IL4:29 +/- 13 pg/ml vs 13 +/- 7; IL2R:1233 +/- 471 U/ml vs 256 +/- 114). Cytokine serum levels were not related with the associated disease, with the CD4+ and CD8+ cells absolute number or with PBL blastogenic in vitro response. The high serum levels of cytokines and IL2R suggest that in AIHA there exist a CD4+ lymphocyte hyperactivation (the low proliferative response of PBL might imply a temporary functional exhaustion of T lymphocytes) as in the other autoimmune diseases.
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PMID:High cytokine serum levels in patients with autoimmune hemolytic anemia (AIHA). 785 62

CFIDS (chronic fatigue and immune disfunction syndrome) is also known as CFS (chronic fatigue syndrome), CEBV (chronic Epstein-Barr virus), M.E. (myalgic encephalomyelitis), yuppie flu and by other names. It is a complex illness characterized by incapacitating fatigue (experienced as exhaustion and extremely poor stamina), neurological problems and a constellation of symptoms that can resemble many disorders, including; mononucleosis, multiple sclerosis, fibromyalgia, AIDS-related complex (ARC) and autoimmune diseases such as lupus. These symptoms tend to wax and wane, but any often severely debilitating and may last for many months or years. All sections of the population (including children) are at risk, but women under 45 seem to be most susceptible. The investigators suggest that CFIDS results from dysfunction of the immune system. The exact nature of this dysfunction is not yet well defined, but it can generally be viewed as an unregulated or overactive state which is responsible for most of the symptoms. There is also evidence of some immune suppression in CFIDS. None of the treatments is consistently satisfactory, but some may be helpful: psychotherapy, physiotherapy, exercise programs, acupunctures, small doses of antidepressants, etc.
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PMID:[The chronic fatigue syndrome]. 790 Apr 53

We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or alpha-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+ cells in culture and interleukin (IL)-1alpha, IL-2, IL-4, tumor necrosis factor (TNF)alpha and soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+ and CD8+ T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+ and PCA1+ B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together. CD4+ T cells were reduced in number in 9 cases, while CD8+ T cells were reduced in 6 cases. The percentage of CD5+ B cells was increased in 5 cases. The percentage of PCA1+ cells was increased in all cases (mean +/- sd: 18 +/- 22 vs 0,2 +/- 1 in controls). The average PBL proliferative response to PHA was reduced (S.I. 71 +/- 55 vs 138 +/- 45 in controls) as well as that to PWM (S.I. 27 +/- 21 vs 75 +/- 24 in controls), despite IL-2 high levels, in all cases, in both sera (mean +/- sd: 648 +/- 351 pg/ml vs 16 +/- 4 pg/ml in controls) and culture supernatants (mean +/- sd: 1045 +/- 677 pg/ml vs 195 +/- 51 pg/ml in controls). In PHA stimulated cultures the percentage of CD25+ cells was reduced (mean +/- sd: 37 +/- 18 vs 63 +/- 14 in controls), sIL-2R levels were like controls in 7 cases. In sera sIL-2R levels were increased in all cases (mean +/- sd: 1256 +/- 465 U/ml vs 256 +/- 114 U/ml in controls), IL-1alpha was increased in all cases too, while IL-4 levels were increased only in 7 cases. Linear regression analysis generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels in supernatants of PHA stimulated culture as well as between S.I. and the percentage of CD25+ cells. Taken together these data suggest a state of B- and T-cell hyperactivation in AIHA. The low PBL proliferative response in vitro, explained in previous studies as a temporary functional exhaustion, might be itself a sign of the complete lymphocyte activation occurring in vivo in AIHA.
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PMID:Lymphocyte activation and cytokine production in autoimmune hemolytic anaemia (AIHA). 902 Apr 7

Antibodies against nucleosomes are a hallmark of systemic lupus erythematosus (SLE). Nucleosomes are uniquely formed during apoptosis, through cleavage of chromatin by nucleases. Increased exposure of nucleosomes to the immune system could play a role in the induction of the autoimmune repertoire in SLE. To determine whether there exists a constitutive defect in the clearance of apoptotic cells, resident peritoneal macrophages from pre-morbid SLE-prone MRL and New Zealand (NZ) mice were analysed for their efficacy to phagocytose apoptotic cells in vitro. Although differences in phagocytic efficacy of up to 50% between different strains of mice were found, these were not related to SLE development. To evaluate whether macrophages from SLE-prone mice are more susceptible to phagocytic 'exhaustion', resident peritoneal macrophages were challenged by 20 h of additional culture in the presence of apoptotic cells. In both lupus and control strains this led to an increased capacity to phagocytose fresh apoptotic cells (increase between 15 and 92%). As a control, macrophages from all strains were also exposed to 20 h of additional culture without apoptotic cells. Under this condition resident peritoneal macrophages from all SLE-prone strains, and of the SLE-parental strain NZB, displayed a significant decrease in their efficacy to phagocytose apoptotic cells (decrease between 16 and 55%). Together, these findings do not support the hypothesis that a constitutive defect in the clearance of apoptotic cells, as evaluated by testing resident peritoneal macrophages, plays an important role in the induction of SLE.
Lupus 2001
PMID:No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal macrophages from pre-morbid lupus mice. 1123 21

Fatigue occurs in many patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases and may be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion. It can be restrictive and severely disabling. We recently found more than 3/4 of systemic lupus erythematosus patients to be significantly affected by this phenomenon. We hypothesized that fatigue in patients with RA might be comparable to sickness behavior in animals possibly caused by disturbances in interleukin-1 beta signaling pathways and thus accessible to blockade by biologic agents. This study compared measures of disease behavior and fatigue symptoms in eight RA patients before and at three time points during treatment with daily administration of anakinra.
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PMID:The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis--a pilot study. 1507 55

Dehydroepiandrosterone (DHEA) therapy is controversial due to sensationalized reports of epidemiologic studies and the over-the-counter availability of DHEA. Human clinical trials have investigated the potential efficacy of DHEA therapy in multiple conditions with resultant inconsistencies in findings. DHEA is unique compared with other adrenal steroids because of the fluctuation in serum levels found from birth into advancing age. The lower endogenous levels of DHEA and DHEA sulfate found in advancing age have been correlated with a myriad of health conditions. Also, some studies suggest gender-specific actions of endogenous and exogenous DHEA. We reviewed only pharmacokinetic studies and human clinical trials investigating the efficacy of DHEA therapy that were placebo-controlled as these provided the most reliable scientific basis for the evaluation of DHEA therapy. Pharmacodynamic studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels, especially in women. These studies report a dose-dependent effect and lack of accumulation of serum androgen levels. Pharmacologic studies also reveal a gender-specific response to DHEA therapy such that testosterone levels are increased in women but not in men. Clinical trials suggest that 50mg of oral DHEA, but not <30mg, can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem, and decrease fatigue/exhaustion. Whereas DHEA replacement therapy may be effective in treating patients with adrenal insufficiency, human clinical trials investigating its efficacy in conditions such as systemic lupus erythematosus, HIV, Alzheimer disease, advancing age, male sexual dysfunction, perimenopausal symptoms, depression, and cardiovascular disease have not provided consistent findings.
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PMID:The use of dehydroepiandrosterone therapy in clinical practice. 1578 47

Psychological stress is believed to be one of the predisposing factors for systemic lupus erythematosus (SLE), whereas physical stress such as exercise has never been reported to be related. We measured the circulating levels of antibodies (IgM, IgG, anti-dsDNA IgG), Th1 (IFN-gamma), Th2 (IL-4, IL-6), and of pro-inflammatory (TNF-alpha, IL-1beta) and anti-inflammatory (TGF-beta) cytokines of C4(-l-) female mice at rest, after acute exercise and after exercise training, using an antibody-capture ELISA. Prior to the exercise, the C4(-l-) mice had higher levels of IgG and anti-dsDNA IgG but lower levels of IFN-gamma, IL-1beta, IL-6 and IL-4 than wild-type C57BL/6 (B6) mice. A single bout of exercise to exhaustion increased serum IgG, TNF-alpha, IL-1beta and TGF-beta in the B6 mice but only TGF-beta in the C4(-l-) mice was increased. We conclude that exhaustive or moderate exercise has no effect on the levels of serum antibodies and cytokines and is thus unlikely to promote the onset of SLE.
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PMID:Serum antibodies and cytokines in C4-deficient mice and their responses to exercise. 2023 74


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