Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant.

The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet''s syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with the high prevalence of thrombosis. This tendency to thrombosis was independent of disease activity of systemic lupus erythematosus. The lupus anticoagulant appears to be a useful marker for a subset of patients with systemic lupus erythematosus at risk for the development of thromboembolic complications.     

Systemic lupus erythematosus in Staphylococcus aureus hyperimmunoglobulinaemia E syndrome.

The prevalence of autoimmune diseases, including systemic lupus erythematosus, is increased in failure of certain host defence mechanisms. Systemic lupus erythematosus, however, has not been recorded as a late complication of the Staphylococcus aureus hyperimmunoglobulinaemia E (hyper-IgE) syndrome. Such a case was investigated in a man suffering from a classic example of the syndrome. Antinuclear antibodies were analysed on a molecular basis. The emergence of immunological and clinical features of systemic lupus erythematosus in patients with defective host defence mechanisms against staphylococcal infections is unlikely to be fortuitous and may help elucidate the pathogenesis of systemic lupus erythematosus. The observations will also aid the long term management of patients with S aureus hyper-IgE syndrome.     

Cardiovascular disease in systemic lupus erythematosus: has the time for action come?

PURPOSE OF REVIEW: The recognition that inflammation is a hallmark of atherosclerotic disease has led to a series of studies reporting accelerated atherogenesis in chronic inflammatory diseases. Indeed, systemic lupus erythematosus is associated with an increased incidence of cardiovascular disease and the etiology thereof deserves closer attention. RECENT FINDINGS: The association between systemic lupus erythematosus and accelerated atherosclerosis has recently been confirmed by surrogate-marker studies for cardiovascular disease in patients with systemic lupus erythematosus. Since the propensity towards cardiovascular disease cannot solely be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors. SUMMARY: In the present review, we will discuss several of these factors as well as their potential impact for future prevention strategies in systemic lupus erythematosus.     

SLE - hematopoietic stem cell transplantation for systemic lupus erythematosus

Hematopoietic stem cell transplantation was first reported for patients with systemic lupus erythematosus in 1997. The procedure has since been performed worldwide including in Europe, in Brazil, and in China. A National Institutes of Health-funded phase III clinical trial of hematopoietic stem cell transplantation for refractory systemic lupus erythematosus is anticipated to begin in 2003. Encouraging responses are raising new hope about the role of adult hematopoietic stem cells in systemic lupus erythematosus.     

PSYCHOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS—A Review of the Literature and Case Reports

In a review of the literature of the last 60 years concerning the association between psychosis and systemic lupus erythematosus, reports of 227 cases of this association were found. The average incidence of psychosis in the various series of systemic lupus erythematosus that were reviewed was 22 per cent. In only 25 per cent of the cases in which the information was given was the psychosis associated with steroid therapy.The psychiatric manifestations are variable and may be associated with a neurological disorder. Psychosis may antedate by many years other features of lupus. The psychosis due to lupus may respond to steroid therapy. Since systemic lupus erythematosus sometimes may be an important differential diagnosis of functional psychosis, appropriate diagnostic studies should be carried out in psychotic patients who have an accelerated sedimentation rate or positive serological test for syphilis without apparent reason.     

Patients with Systemic Lupus Erythematosus Have Higher Prevalence of Thyroid Autoantibodies: A Systematic Review and Meta-Analysis

Background

Thyroid autoimmunity is considered the most common type of organ-specific autoimmune disorder and can be associated with other autoimmune endocrine disorders or non-endocrine diseases. Systemic lupus erythematosus is a prototypical autoimmune disorder with multifactorial etiology. The pathogenesis and development of the disease may result from a loss of immune tolerance and the resulting synthesis of autoantibodies against nuclear antigens. Autoimmune factors may be common features of both thyroid autoimmunity and systemic lupus erythematosus, making it likely that both conditions may coexist within some patients.

Methods and Findings

A number of studies have investigated whether an association between thyroid autoimmunity and systemic lupus erythematosus exists. However, the results of these studies have been inconsistent. Furthermore, most of these studies have had relatively small sample sizes, which have rendered them insufficiently powerful to determine whether there is an association between systemic lupus erythematosus and thyroid autoimmunity. The main objective of this meta-analysis is to provide reliable estimates of the extent of any association between thyroid autoimmunity and systemic lupus erythematosus by combining the primary data from all relevant studies. Literature databases were searched, including the Medline, Embase, Web of Science, Chinese Wanfang and CBM databases, from January 1970 to May 2014. A total of 1076 systemic lupus erythematosus cases and 1661 healthy controls were included in this study. From these data, the odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis results showed that the prevalence of thyroid autoantibody positivity in patients with systemic lupus erythematosus was higher than in healthy controls (TgAb: OR = 2.99, 95% CI = 1.83–4.89; TPOAb: OR = 2.20, 95% CI = 1.27–3.82, respectively).

Conclusion

The results of this meta-analysis suggest that thyroid autoimmunity is more prevalent in patients with systemic lupus erythematosus than in a control group.     

SLE – Hematopoietic stem cell transplantation for systemic lupus erythematosus

Hematopoietic stem cell transplantation was first reported for patients with systemic lupus erythematosus in 1997. The procedure has since been performed worldwide including in Europe, in Brazil, and in China. A National Institutes of Health-funded phase III clinical trial of hematopoietic stem cell transplantation for refractory systemic lupus erythematosus is anticipated to begin in 2003. Encouraging responses are raising new hope about the role of adult hematopoietic stem cells in systemic lupus erythematosus.     

Studies on precipitating and hemagglutinating antibodies in systemic lupus erythematosus

We studied the precipitating and hemagglutinating autoantibodies in the sera of patients with various connective tissue diseases in general and lupus in particular. Saline soluble extract of goat thymus had adequate antigenic materials as compared to other organs. Twenty per cent of patients with systemic lupus erythematosus were positive for precipitating autoantibodies by immunodiffusion and 44% by counterimmunoelectrophoresis. Normal human subjects, nonrheumatic disease patients and patients with rheumatoid arthritis and progressive systemic sclerosis were all negative. Forty seven per cent of positive systemic lupus erythematosus sera showed two precipitin systems. Enzyme sensitivities were used as the basis of identification of most of the antigenic specificities. Passive hemagglutination was carried out to identify antibodies to non-histone nuclear protein and nuclear ribonucleo-protein antigens. Thirty eight % of systemic lupus erythematosus patients were positive by this technique. Passive hemagglutination although a highly sensitive technique could not detect antibodies against antigenic systems other than non-histone nuclear protein and nuclear ribonucleoprotein.     

Acute acalculous cholecystitis complicating systemic lupus erythematosus: case report and review.

A case of acalculous cholecystitis presented as an acute abdominal emergency in a 22 year old woman with severe systemic lupus erythematosus. At the time of presentation the patient was receiving high doses of prednisone and cyclophosphamide to control her underlying disease. Histological examination of the biopsy specimen from the gall bladder showed lupus vasculitis. This complication of systemic lupus erythematosus has not been reported before. Laboratory studies and changes in lupus activity may fail to predict the onset of cholecystitis.     

Allergic diseases,drug adverse reactions and total immunoglobulin E levels in lupus erythematosus patients

BACKGROUND: The association of allergic diseases, drug adverse reactions and elevated total immunoglobulin E (IgE) concentration in systemic lupus erythematosus patients remains controversial. The aim of the study was to investigate the prevalence of those features in active and inactive systemic lupus erythematosus patients, and in the control group as well. METHODS: Total IgE concentration was evaluated by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSIONS: The results of our study revealed that concomitant allergic diseases were not more frequent in systemic lupus erythematosus patients than in the general population. Total IgE concentration was significantly higher during the active stage of the disease. Drug reactions were very frequent but not connected with IgE elevation. Our results indicate that IgE may play a role in lupus pathogenesis, especially in the active phase of the disease.     

Disturbances of apoptotic cell clearance in systemic lupus erythematosus

Systemic lupus erythematosus is a multifactorial autoimmune disease with an as yet unknown etiopathogenesis. It is widely thought that self-immunization in systemic lupus is driven by defective clearance of dead and dying cells. In lupus patients, large numbers of apoptotic cells accumulate in various tissues including germinal centers. In the present review, we discuss the danger signals released by apoptotic cells, their triggering of inflammatory responses, and the breakdown of B-cell tolerance. We also review the pathogenic role of apoptotic cell clearance in systemic lupus erythematosus.     

Cytological Aspects of Pleural, Peritoneal and Pericardial Fluids From Patients With Systemic Lupus Erythematosus

Serous effusions of nine of 33 patients with systemic lupus erythematosus contained lupus erythematosus (LE) cells, identifiable in Papanicolaou-stained smears, wet films stained with toluidine blue, and cell blocks stained with haematoxylin and eosin. Specimens in which LE cells were found contained at least a moderate number of polymorphonuclear neutrophilic leucocytes. Most specimens containing LE cells also contained cells that resembled LE cells (tart cells), which appeared to be small macrophages that had phagocytosed a non-homogenized nucleus of a cell that had undergone degeneration. In 34 years of cytologic practice we have recognized LE cells in serous effusions only from patients who were already diagnosed as having systemic lupus erythematosus.     

Regulatory T cells in systemic lupus erythematosus: past,present and future

Regulatory/suppressor T cells (Tregs) maintain immunologic homeo-stasis and prevent autoimmunity. In this article, past studies and recent studies of Tregs in mouse models for lupus and of human systemic lupus erythematosus are reviewed concentrating on CD4⁺CD25⁺Foxp3⁺ Tregs. These cells consist of thymus-derived, natural Tregs and peripherally induced Tregs that are similar phenotypically and functionally. These Tregs are decreased in young lupus-prone mice, but are present in normal numbers in mice with established disease. In humans, most workers report CD4⁺Tregs are decreased in subjects with active systemic lupus erythematosus, but the cells increase with treatment and clinical improvement. The role of immunogenic and tolerogenic dendritic cells in controlling Tregs is discussed, along with new strategies to normalize Treg function in systemic lupus erythematosus.     

Reversal of aplastic anaemia secondary to systemic lupus erythematosus by high-dose intravenous cyclophosphamide

Aplastic anaemia is rare as a primary feature of systemic lupus erythematosus and is more commonly a complication of treatment with cytotoxic drugs. Three years after starting treatment for systemic lupus erythematosus a 22-year-old woman developed bone-marrow depression. Azathioprine was thought to be responsible and was withdrawn. The aplastic anaemia worsened despite treatment with prednisolone. In view of clinical and serological evidence of lupus disease activity the patient was given high-dose intravenous cyclophosphamide and the aplastic anaemia responded in a sustained manner.In such cases of continued disease activity high-dose immunosuppressive agents may prove effective.     

Vasculitis: mechanisms involved and clinical manifestations

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.     

Physical criteria of pathological processes. III. Structure of the correlation between the level of steady brain potential with serum complement proteins in rheumatic diseases]

The activity of serum complement proteins and the level of steady brain potential in patients with systemic lupus erythematosus and rheumatoid arthritis were determined. The statistical analysis indicated that there is a correlation between the parameters of the complement system and neurophysiological characteristics. The differences between rheumatoid arthritis and systemic lupus erythematosus are observed in the mean values of activity of complement proteins and the steady potential, their dispersions, and the structure of correlations between immunological and neurophysiological parameters.     

Anti-elastin antibodies in systemic lupus erythematosus

Immunological response to elastin-derived peptides may cause tissue damage with subsequent degradation of the elastic fibres. Therefore, an incidence of anti-elastin antibodies in sera of patients with the systemic lupus erythematosus was studied. Sixty sera from 50 patients with systemic lupus erythematosus and 50 healthy subjects were assayed with dot-immunobinding technique. Titre 1:10 was considered diagnostically significant. Anti-elastin antibodies were diagnosed in 19 patients (31%) where as they were absent in the control group. In all cases anti-elastin antibodies were IgG.     

Deletion of IL-18 Expression Ameliorates Spontaneous Kidney Failure in MRLlpr Mice

The role of IL-18 in the pathogenesis of systemic lupus erythematosus is still not definitively solved. In this study, we generated MRL^lpr mice, which develop a disease resembling systemic lupus erythematosus, genetically devoid of IL-18 expression. These mice in comparison to IL-18-competent MRL^lpr mice show reduced signs of renal pathogenesis, while other parameters such as mean survival time, lymphadenopathy, constitutive interferon-γ production, and frequency of CD3⁺B220⁺ abnormal T cells were without differences. We conclude that in the systemic lupus erythematosus syndrom IL-18 is involved specifically in the renal pathogenesis.     

Developments in the clinical understanding of lupus

Advances in genetics and new understanding of the molecular pathways that mediate innate and adaptive immune system activation, along with renewed focus on the role of the complement system as a mediator of inflammation, have stimulated elaboration of a scheme that might explain key mechanisms in the pathogenesis of systemic lupus erythematosus. Clinical observations identifying important comorbidities in patients with lupus have been a recent focus of research linking immune mechanisms with clinical manifestations of disease. While these advances have identified rational and promising targets for therapy, so far the therapeutic trials of new biologic agents have not met their potential. Nonetheless, progress in understanding the underlying immunopathogenesis of lupus and its impact on clinical disease has accelerated the pace of clinical research to improve the outcomes of patients with systemic lupus erythematosus.