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PubMed2000

Stenosis of a mechanical mitral prosthetic valve in a patient with systemic lupus erythematosus.

A young woman with systemic lupus erythematosus (SLE) developed progressive heart failure several years after mitral valve replacement with a Björk-Shiley prosthesis for treating mitral stenosis due to Libman-Sacks endocarditis. She was admitted to the hospital with pulmonary oedema. Transoesophageal echocardiography revealed stenosis of the mitral prosthesis, which was covered by fibrous tissue. Replacement of the prosthesis was done but the patient died from cerebral haemorrhage three days later. Although three cases of prosthetic valve dysfunction in SLE have been documented so far, this is to our knowledge the first report of a SLE recurrence on a tilting disc mechanical valve.

Adult↗

PubMed2006

Signaling abnormalities in systemic lupus erythematosus as potential drug targets.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by T-cell, B-cell, and dendritic cell dysfunction and antinuclear autoantibody production. Much of the knowledge that has been gained about SLE in recent years is related to molecular signaling abnormalities present in the disease. Signaling through the T-cell receptor (TCR) is affected in SLE by alterations in the localization, amount, and activity of numerous protein kinases. TCR stimulation releases calcium from intracellular stores, which triggers an influx of extracellular calcium and activates the transcription of many genes, including interleukin-2. Short-term calcium fluxing is exaggerated in SLE, but long-term calcium fluxing is diminished and may account for sub-optimal interleukin-2 production. SLE T-cells have persistently hyperpolarized mitochondria associated with increased mitochondrial mass, high levels of reactive oxygen species (ROS) and low levels of ATP, which decrease activation-induced apoptosis and instead predispose T cells for necrosis, thus stimulating inflammation in SLE. The pentose phosphate pathway impacts the mitochondrial potential and represents a target for possible intervention. Nitric oxide (NO) is a potential link to tie together the signaling and mitochondrial abnormalities in SLE. NO-induced mitochondrial biogenesis recapitulates the TCR-stimulated calcium fluxing abnormalities of SLE T-cells. Since mitochondria can store calcium, the increase in mitochondrial mass may be implicated in the aberrant calcium fluxing in SLE T cells. The mammalian target of rapamycin senses the mitochondrial potential and regulates calcium release, serving as a novel target of treatment of SLE.

Adenosine Triphosphate↗

PubMedDate not supplied

Systemic lupus erythematosus in pregnancy--case report.

Systemic lupus erythematosus (SLE) is a chronic inflammatory connective tissue disease commonly diagnosed after the age of 20, mostly around the age of 30 years. It is more common in women than in men, especially during the fertile period. Women with SLE are at higher risk for spontaneous abortions, intrauterine fetal death, preeclampsia and eclampsia, preterm delivery and intrauterine growth retardation. This paper is a case report of a pregnant woman with SLE complicated with preeclampsia, but it also discusses follow-up of such pregnancies.

Adult↗

PubMed1996

Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective.

Vascular damage in systemic lupus erythematosus (SLE) occurs through vasculitis, premature atherosclerosis, and hypercoagulability (predominantly due to the antiphospholipid antibody syndrome). In the Hopkins Lupus Cohort, a prospective cohort study, the incidence of thrombosis is 2 per 100 person-years of follow-up. Markers of immune-complex mediated injury (high anti-dsDNA and low C3), atherosclerosis (hypertension, hyperlipidemia, homocysteine) and antiphospholipid antibodies (lupus anticoagulant or anticardiolipin) are independent predictors of thrombosis. Hydroxychloroquine use is protective against future thrombosis.

Cohort Studies↗

PubMed2005

Successful treatment of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus.

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.

Adrenal Cortex Hormones↗

PubMed2000

Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus.

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at high frequencies in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27(high) plasma cells and naive CD27(-) B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27(+) B cells coexpressing IgD were memory B cells preferentially using V(H)3 family members with multiple somatic mutations. CD27(high) plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V(H)4 family members. These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.

ADP-ribosyl Cyclase↗

PubMed2005

CD226 expression deficiency causes high sensitivity to apoptosis in NK T cells from patients with systemic lupus erythematosus.

Humans and mice with systemic lupus erythematosus (SLE) and related autoimmune diseases have reduced numbers of NK T cells. An association between NK T cell deficiency and autoimmune disease has been identified. However, the mechanisms for reduction of NK T cell number in patients with SLE are unknown. In the present study we report that NK T cells from active SLE patients are highly sensitive to anti-CD95-induced apoptosis compared with those from normal subjects and inactive SLE patients. CD226 expression is deficient on NK T cells from active SLE patients. The expression of one antiapoptotic member protein, survivin, is found to be selectively deficient in freshly isolated NK T cells from active SLE patients. CD226 preactivation significantly up-regulates survivin expression and activation, which can rescue active SLE NK T cells from anti-CD95-induced apoptosis. In transfected COS7 cells, we confirm that anti-CD95-mediated death signals are inhibited by activation of the CD226 pathway through stabilization of caspase-8 and caspase-3 and through activation of survivin. We therefore conclude that deficient expression of CD226 and survivin in NK T cells from active SLE is a molecular base of high sensitivity of the cells to anti-CD95-induced apoptosis. These observations offer a potential explanation for high apoptotic sensitivity of NK T cells from active SLE, and provide a new insight into the mechanism of reduction of NK T cell number in SLE and understanding the association between NK T cell deficiency and autoimmune diseases.

Adolescent↗

PubMedDate not supplied

Dexamethasone-cyclophosphamide pulse therapy in systemic lupus erythematosus.

BACKGROUND AND AIMS: Therapy systemic lupus erythematosus (SLE) has been generally discouraging. Methyl-prednisolone pulse therapy has been used for various connective tissue disorders. We used intravenous dexamethasone cyclophosphamide pulse therapy to treat SLE. METHODS: Fourteen patients (10 females and 4 males) between the age of 15-48 years with definite or classical clinical criteria laid by American Rheumatism Association criteria were treated by Dexamethasone-Cyclophosphamide pulse (DCP) therapy at our center. RESULTS: It was possible to induce a complete clinical remission with DCP therapy in most of the patients thereby offering them life free from disease and drugs. The side effects commonly observed with conventional daily dose regimen of corticosteroids were not present or were mild. CONCLUSIONS: Almost all patients had good response after 3-4 pulses to allow them a normal life style. Fever, malar rash and oral ulceration responded early but photosensitivity, discoid rash, alopecia and joint pains took some more time.

Adolescent↗

PubMed1984

NIH conference. Systemic lupus erythematosus: insights from animal models.

Systemic lupus erythematosus is a multisystem, antibody-mediated, autoimmune disorder that occurs spontaneously in humans and mice. Genetic factors appear to play an important predisposing role in the disorder: The presence of certain genes may produce a generalized immune abnormality, whereas others may lead to specific autoantibodies. Environmental triggers increase autoantibody production and augment the expression of illness. Bacterial and viral illnesses can provide stimulation by activating macrophages and T cells that, in turn, stimulate B cells. In the absence of normal control mechanisms, the stimulatory process is not suppressed, and excessive stem cell proliferation results in abnormal B-cell proliferation. A trigger for the disease is the signaling of the proliferating B cells to differentiate into antibody-forming cells. Most autoantibody-producing B cells can be eliminated from mice with lupus erythematosus by virtue of the presence of the gene, xid. In addition, administration of an analog of arachidonic acid is an effective treatment for murine lupus erythematosus.

Animals↗

PubMed1987

Synchronization of plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus.

Two patients with severe systemic lupus erythematosus, who had not responded to conventional therapy, were treated with plasmapheresis and subsequent pulse cyclophosphamide. This approach uses the plasmapheresis-induced proliferation of pathogenic clones for partial clonal deletion by giving large doses of cytotoxic drugs during the assumed period of increased B-cell vulnerability. Both patients had a rapid and distinct improvement in clinical symptoms and laboratory parameters, including the control of a life-threatening case of lupus pneumonitis. Their conditions were stabilized by giving low-dose cyclophosphamide for the next 6 months. At 14-month follow-up, there were no clinical signs of relapse.

Administration, Oral↗

PubMedDate not supplied

Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus.

OBJECTIVE: Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred not only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively signalling molecule CTLA-4 is involved in establishing and maintaining of peripheral T cell tolerance, which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses. We tested if there was an association between CTLA-4 and SLE, a disease with B and T cell hyperreactivity and impaired peripheral T cell tolerance. METHODS: Using the polymerase chain reaction--restriction fragment length polymorphism method with Bbv I digestion, we assessed an exon 1 transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls. RESULTS: The distribution of CTLA-4 exon 1 genotypes in the SLE group was significantly different from that in the controls (chi 2 = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homozygotes vs 53.9% of the controls. The frequency of the G allele was significantly higher in SLE patients (35.8%) than in controls (25.7%; chi 2 = 4.142, p = 0.042). CONCLUSION: Our results indicate that the non-MHC linked CTLA-4 gene could confer susceptibility in SLE, as it does in various other autoimmune diseases (Hashimoto thyroiditis, Graves' disease, IDDM).

Abatacept↗

PubMed2000

Systemic lupus erythematosus: a multisystem autoimmune disorder.

Systemic lupus erythematosus (SLE) is a chronic illness that has no known cause. As an autoimmune, inflammatory disease, it can affect various organs in different ways. Because of its fluctuating, unpredictable qualities, it requires the implementation of physiologic and psychosocial interventions that may change daily. A plan of care unique to each individual with SLE is essential to its management.

Adrenal Cortex Hormones↗

PubMed2000

Accurately describing changes in disease activity in Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores correlate with the clinician's impression of level of disease activity. METHODS: In total, 230 patients with SLE followed at the University of Toronto Lupus Clinic who had 5 visits 3 months apart in 1992-93 were studied. At each visit a standard protocol was completed. A clinician who did not know the patients or their SLEDAI scores evaluated each patient record and assigned a clinical activity level. "Flare" was defined by new or increased therapy for active disease, an expression of concern, or use of the term "flare" in the physician's notes. The SLEDAI score was calculated from the database. RESULTS: SLEDAI scores described a range of clinical activity as recognized by the clinician. Median SLEDAI scores ranged from 2 (inactive disease) to 8 (persistently active or flare). When the clinician assessed the patient to be improved, the median SLEDAI score decreased by 2. When the clinician assessed that the patient was experiencing a flare, the SLEDAI score increased by a median of 4. CONCLUSION: Based on our data we propose the following outcomes for patients with SLE: flare, an increase in SLEDAI > 3; improvement is a reduction in SLEDAI of > 3; persistently active disease is change in SLEDAI +/- 3; and remission a SLEDAI of 0. These outcomes will allow a more complete description of a patient's response to therapeutic intervention in a responder index.

Adolescent↗

PubMedDate not supplied

[Indices of disease activity in systemic lupus erythematosus. Review of the literature].

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of autoantibodies reacting with many different self antigens. The analysis of clinical expression and evolution of this disease is a milestone in the definition of therapeutic strategies. A parameter universally accepted as gold standard is lacking so far. About 60 indices for defining and measuring the activity of this disease have been proposed in the last 20 years. The most important of these are discussed in this review, focusing both on their role in the evaluation and outcome of patients and on the main studies assessing their validity and reliability.

Humans↗

PubMed2001

Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.

The serological hallmark of systemic lupus erythematosus (SLE) is the presence of antibodies against double-stranded DNA. However, several studies have suggested that it is not DNA itself, but nucleosomes that are the immunogenic particles involved both in the induction of anti-DNA antibodies, and in the pathophysiology of SLE. Meanwhile, It has been demonstrated that there is an accelerated in vitro apoptosis of lymphocytes from patients with SLE. Therefore, one can postulate that the process of apoptosis may provide a source of nuclear antigens to drive the autoantibody response seen in SLE. Our study has demonstrated that hydroxychloroquine exhibits an anti-apoptotic action and this anti-apoptotic effect is dependent on monocyte coexistence. We used both morphology assessment and fluorescent antibody cell sorter (FACS) analysis to measure the apoptotic percentage of lymphocytes from 25 SLE patients in medium alone (control) or with the addition of different concentrations of hydroxychloroquine. Our results have shown that there is a significant decrease in the percentage of apoptosis at the therapeutic concentration (10(-6) M) as compared with the control (p < 0.05). It has been reported that the anti-rheumatic properties of hydroxychloroquine result from its interference with antigen processing in macrophages and other antigen-presenting cells. We propose that this results in decreased stimulation of autoreactive lymphocytes reactive with self-peptides, and consequently diminution of activation-induced cell death (apoptosis) of mature peripheral lymphocytes.

Acridine Orange↗

PubMed2002

Trends in deaths from systemic lupus erythematosus--United States, 1979-1998.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease of unknown etiology that can affect several organs. Because SLE affects connective tissues and because painful joints and arthritis are among its most common manifestations, this disease is classified with arthritis and other rheumatic diseases. SLE is one of the more fatal forms of rheumatic diseases and non-Causcasian race is a risk factor for death from SLE; however, trends in death from SLE have not been analyzed recently. To characterize deaths from SLE, CDC reviewed SLE deaths during 1979-1998. This report presents the results of that analysis, which indicate that marked age-, sex-, and race-specific disparities exist in SLE death rates and that death rates have increased by approximately 70% during the study period among black women aged 45-64 years. Prevention of deaths requires early recognition and diagnosis of SLE and appropriate therapeutic management.

Adolescent↗

PubMed2002

Controversies and advances in the management of systemic lupus erythematosus in children and adolescents.

Systemic lupus erythematosus (SLE) begins in childhood or adolescence in approximately 15% of cases, and although short- and long-term outcomes have improved considerably in the past 20 years there remain many areas of controversy regarding optimal management of these patients. In this chapter, areas of debate reviewed include: the appropriate timing of adding immunosuppressive therapy to corticosteroids, the optimal choice of immunosuppressive medication, the management of patients who fail 'standard' therapies, the significance and appropriate treatment of antiphospholipid antibodies in children with SLE and the emerging morbidities of childhood SLE. The goal of this chapter is to provide a balanced literature review and clinical approach to children and adolescents with SLE and to highlight areas requiring studies in paediatric clinical research.

Adolescent↗

PubMed2002

Atherosclerotic vascular disease in systemic lupus erythematosus.

In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority.

Black or African American↗