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Association between IFNA genotype and the risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by multisystem inflammation and production of autoantibodies, which can generate immune complexes and may cause tissue damage through the recognition of an autoantigen. Although many factors have been proposed, such as genetic factors, environmental factors, hormonal action, viruses, and dysregulation of cytokine production, the cause of this disease is not well understood. It has been reported that the levels of interferon (IFN)-alpha in the sera of some SLE patients are elevated and that IFN-alpha induces maturation of monocytes into highly active antigen-presenting dendritic cells (DCs). We analyzed the association between IFN-alpha genotype and the risk of SLE to clarify whether IFN-alpha plays a central role in susceptibility to SLE. The results showed that no IFN-alpha genotype was significantly associated with the risk of SLE.

Adolescent↗

Variable atrioventricular block in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of auto-antibodies and immune complexes, can affect all organs including the heart. The involvement of the conduction system in SLE has been less commonly described. We report a case of an asymptomatic 45-year-old woman with SLE referred to the emergency department (ED) for thrombocytopenia, and was found to have alternating first- and second-degree atrioventricular block (AVB) during routine electrocardiographic screening for hospital admission. Serial electrocardiograms (ECG) done in the ED when compared to those recorded 24 h prior revealed progression from mild first-degree AVB (PR interval = 216 ms) to significant first-degree AVB (PR interval = 510 ms), followed by second-degree AVB (Mobitz type I-Wenckebach phenomenon). The conduction abnormalities recorded over a 28-h period resolved with corticosteroid treatment. Review of the literature on the disruption of the cardiac conduction system in SLE is discussed.

Electrocardiography↗

Tumor necrosis factor receptor II (TNFRII) exon 6 polymorphism in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that exhibits extensive clinical heterogeneity. Several studies have suggested a role for tumor necrosis factor alpha (TNFalpha) in SLE and recently, the locus encompassing the TNF receptor II (TNFRII), which is a mediator of TNF effect, was amongst the candidate loci suggested by genetic linkage studies of multi-case SLE families. Komata et al. reported an association between a polymorphism at position 196 (R allele) of TNFR II and SLE in Japanese patients. We have typed SLE patients from two different ethnic populations, Spanish and UK Caucasoids, for this polymorphism using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)-based technique. No significant differences in allele or genotype frequencies were found between cases and matched controls in either population. The TNFRII 196R allele does not appear to be associated with SLE susceptibility in either Spanish or UK populations.

Alleles↗

Systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) of childhood is a complex and challenging disease which can occur at any age. Identification of disease early in it's course and aggressive, appropriate management leads to improved outcome for an individual child. The history of SLE indicates how much progress has been made in the last quarter century. A discussion of the etiopathogenesis of SLE demonstrates the complexity of the syndrome. This is followed by a description of clinical manifestations, including diagnostic criteria, differential diagnosis and suggested methods for eliciting important symptoms to make the diagnosis. Evaluation of specific organs is next reviewed highlighting critical organ manifestations that are significant for future prognosis. Treatment of SLE includes a variety of medications, including non-steroidal anti-inflammatory medications, steroids and immuno-suppressive drugs. Attention to physical activity, stress and nutrition is equally important. Signs and symptoms that indicate disease flare or infection are described. Lastly, related syndromes are reviewed.

Adrenal Cortex Hormones↗

Haplotype analysis of tumour necrosis factor receptor genes in 1p36: no evidence for association with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with partially understood aetiology. The 1p36 region has been previously linked with SLE and harbours tumour necrosis factor receptor (TNFR) genes. Functional and genetic data implicate their gene products in SLE and other autoimmune diseases. In all, single-nucleotide polymorphisms (SNPs) across TNFRSF14 (HVEM), and 43 SNPs across the TNFRSF8 (CD30) and TNFRSF1B (CD120B) locus were investigated for linkage disequilibrium (LD) and haplotype analysis in European-Caucasians. Strong LD was observed across HVEM and CD120B, and little LD and recombination across CD30. We also examined the association of SNPs and haplotypes in HVEM, CD30 and CD120B with SLE in European-Caucasians. There was no evidence of association for these genes in 456 European-Caucasian families with SLE from UK. Haplotype tagging SNPs are made known across areas of strong LD, which will facilitate analysis for susceptibility in other diseases.

Chromosomes, Human, Pair 1↗

Prothymosin alpha restores the depressed autologous and allogeneic mixed lymphocyte responses in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a variety of profound T-cell abnormalities among which are decreased autologous and allogeneic mixed lymphocyte reactions (auto-MLR and allo-MLR, respectively). In a group of 10 patients with SLE, the mean auto-MLR and allo-MLR responses, tested by tritiated thymidine incorporation, were significantly decreased. If optimal doses of highly purified prothymosin alpha (ProT alpha) were present during the auto- of allo-MLR, the T-cell proliferative responses of SLE patients were increased to normal levels. ProT alpha had more pronounced enhancing effect in patients than in normal individuals. Among patients, ProT alpha was more effective in those who had active disease and low proliferative responses. These results demonstrate that ProT alpha can fully restore the deficient T-cell proliferative responses in auto- and allo-MLR in patients with SLE. ProT alpha, or a certain peptidic fragment of it, could prove potentially useful in the treatment of SLE.

Adjuvants, Immunologic↗

The homogeneous multiplexed system--a new method for autoantibody profile in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method. We analyzed the presence of elevated titers of anti-Ro, anti-La, anti-RNP, anti-Sm, anti-Jo1, anti-centromere, anti-Scl-70, anti-histone, and anti-dsDNA antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We compared the type, level and number of autoantibodies and the correlation between the autoantibody profile and disease severity utilizing the SLEDAI score. Elevated titers of at least one autoantibody were detected in 48% of 42 SLE patients. Elevated titers of anti-Ro antibodies were most commonly detected. The distribution of specific autoantibodies was: anti-Ro- 23.8%, anti-dsDNA- 19%, antihistone- 19%, anti-RNP- 14.2%, anti-La antibodies- 11.9%, anti-Sm- 7.1%, anti-Scl 70-4.7%, and anti-centromere- 2.4%. Utilizing ROC analysis, the sensitivity and specificity of anti-DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and 79.4% respectively. Elevated titers of anti-Jo1 antibody were not detected. There was a correlation with the titer of anti-Ro antibodies and disease activity by the SLEDAI score. Seven patients harbored one autoantibody only, 15 patients harbored 2-3 autoantibodies, 3 patients harbored 4-5 autoantibodies, and one patient harbored 6 autoantibodies. A correlation between the number of autoantibodies per patient and disease severity was found. One patient with a multitude of autoantibodies had severe lupus and a myriad of clinical manifestations. In conclusion, the multiplex system is specific and sensitive, provides an autoantibody profile in a single test, and may be useful as a diagnostic test for SLE. Elevated anti-Ro antibodies are associated with severe disease. An autoantibody load may be indicative of more severe disease.

Antibodies, Antinuclear↗

A meta-analysis of the clinical manifestations of older-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) with onset in later life has been reported to have a clinical presentation different from that in younger individuals; however, the disease manifestations typical of older-onset SLE patients are known to vary widely among published studies. Meta-analysis is a statistical process capable of quantitatively combining the results of these reports. This meta-analysis examines the methodologic features of studies investigating age-associated manifestations of SLE, and pools estimates of association between clinical features of SLE and age across these studies. Serositis, interstitial pulmonary disease, anti-La antibodies, and Sjögren's syndrome were most strongly and consistently associated with older-onset SLE, while alopecia, Raynaud's phenomenon, fever, lymphadenopathy, hypocomplementemia, and neuropsychiatric illness were present less frequently in this group. The extent to which information bias, selection bias, and uncontrolled confounding effects potentially influence these results is discussed. The available information in the literature does not describe the spectrum of clinical manifestations of SLE in the elderly sufficiently to allow its categorization as a distinct entity.

Age Factors↗

Quality of life in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a pervasive disease with wide-ranging effects on physical, psychological and social well-being. As such, a comprehensive assessment of SLE should include several different outcomes, such as quality of life (QoL) and economic costs, in addition to measures of disease activity and damage. In fact, disease effects on QoL are often considered of greater overall importance to patients. Two approaches have been used in the measurement of QoL: generic questionnaires and disease-specific questionnaires. Generic questionnaires are designed to be used across various conditions and populations, whereas disease-specific questionnaires are designed to measure outcomes in one specific disease or condition. The most commonly used measure of QoL is the Medical Outcomes Study Short Form 36 (SF-36), which is a generic measure that is applicable in a variety of conditions, including SLE. Recently, SLE-specific measures have been developed that may prove to be more responsive than generic measures. The hope is that improved outcome measures will allow for better assessment of SLE and eventually facilitate drug development and improve patient care.

Humans↗

C-fibre function in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) frequently involves the central nervous system (CNS), but to a considerably lesser degree leads to peripheral neuropathy as measured by conventional nerve conduction velocity studies. Neuropathic symptoms are, however, frequently reported. Abnormalities of other nerve fibers than the large myelinated nerves might thus be responsible for such phenomena. Three age matched groups of 44 patients with SLE, 50 patients with rheumatoid arthritis (RA) and 45 healthy controls were investigated with quantitative sensory thermotesting. Warm detection thresholds (WDT) and heat pain detection thresholds (HPDT) were found significantly higher in SLE compared to RA and controls. There were no differences between the RA and the control group. In the SLE group no association to disease duration, medication or CNS abnormalities were found. Neuropathic symptoms and vibration thresholds showed weak associations to WDT. These findings imply that there is an impairment of C-fibre function in SLE. This small fibre neuropathy is probably not part of a generalized diffuse polyneuropathy also affecting large fibres, although this can not be ruled out completely by this study.

Adult↗

Painless massive ascites and hypoalbuminemia as the major manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is frequently associated with ascites, but rarely without proteinuria. We report a 10-year-old girl with distended, non-tender abdomen with shifting dullness and no pitting edema in the lower legs before admission. Facial rash had appeared 1-2 weeks before admission and became more prominent 3 days prior to admission. Hypoalbuminemia with hypertriglycemia (but no proteinuria or diarrhea) was noticed. The antinuclear antibody titer was 1:2560 (speckle type) and the anti-double-stranded DNA was 1:160. Abdominal echo revealed no cirrhosis change or venous obstruction. Chest X-ray and electrocardiogram revealed no cardiomegaly or pericardial effusion. The serum prealbumin was low on admission day 5, but the liver function tests were within normal range. We deduced that the hypoalbuminemia in SLE without nephritis may be secondary to mesenteric vascular leakage. SLE may present with initial manifestation of painless massive ascites. Careful utilization of history taking, chest X-ray, electrocardiogram, cardiac and abdominal echo, urinary analysis and serum prealbumin is helpful in decision-making while assessing such patients.

Ascites↗

A practical guide to systemic lupus erythematosus.

Systemic lupus erythematosus is a challenging disease with varied manifestations resulting from widespread immune complex deposition. It may present in the general pediatric office as an acute illness with fever, rash, and hematuria, or as chronic fatigue and malaise that might be mistaken for "school phobia". Although SLE remains an infrequent disease in general pediatric practice, mild cases are more frequent than was previously recognized. These children benefit from therapy if the physician is alert to their occurrence and makes the appropriate diagnosis. The understanding of the role of genetics and environmental agents in the pathogenesis of SLE has improved over the past 10 years. In addition, the past 10 years have seen refinements in the use of immunosuppressive regimens, such as cyclophosphamide, that have led to both improved quality of life and improved survival for children with active SLE unresponsive to corticosteroids. Although long-term concerns regarding the safety and efficacy of immunosuppressive drug regimens persist, the future is increasingly bright for children with SLE who receive appropriate care in a timely fashion.

Adolescent↗

Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.

Brain Diseases↗

[Clinical features of Pneumocystis pneumonia in patients with systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is often associated with various opportunistic infections, particularly during treatment with corticosteroids or immunosuppressants. We studied the clinical characteristics of 15 patients with SLE who underwent diagnostic bronchoalveolar lavage (BAL) and compared 6 patients with confirmed Pneumocystis pneumonia (PcP+), with 9 patients without Pneumocystis pneumonia (PcP-). The serum concentrations of beta-D-glucan and KL-6 were significantly higher in PcP+ than in PcP- patients, whereas serum LDH was similar in both groups. The serum concentrations of complement, a marker of SLE activity, and of IgG did not predict the presence of PcP. In all patients, the overall cell and lymphocyte counts were increased in the BAL fluid, without any significant difference between the PcP+ and PcP- groups. Ground-glass opacities on chest computed tomography, and oxygenation impairment (PaO2/FiO2<200Torr) were more common in PcP+ than PcP- patients. We concluded that, in patients with SLE, serum beta-D-glucan and KL-6 might be useful in the diagnosis of PcP, particularly when severe hypoxemia precludes BAL.

Adult↗

Antibodies to vascular heparan sulfate proteoglycan in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease which involves the basement membranes of blood vessels in multiple organs. An important component of the microvasculature is vascular heparan sulfate proteoglycan (HSPG). In this study, we investigated the presence in SLE and other immune disease sera of autoantibodies to purified vascular HSPG. Our data demonstrate that antibody to HSPG is found primarily in SLE sera, and not in sera from controls or patients with other immune diseases. The titer of antibody to HSPG correlated with complement depletion in SLE sera. Antibody to HSPG was frequently found in high titer in SLE patients with renal and neurologic involvement. These studies indicate that our assay for antibody to vascular HSPG detects a pathologically relevant autoantibody in SLE sera. The implications of our findings for pathogenesis of vascular autoimmunity are discussed, including the relationship of anti-vascular HSPG antibody to anti-DNA and antiphospholipid antibodies.

Administration, Topical↗

Effects of prolactin in stimulating disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced by hormones. High prolactin concentrations were associated with early death from autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW mice that delivered and nursed pups and those that underwent pseudopregnancy had changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin-suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin concentrations are reported in SLE patients of both sexes. We found four women with long-standing hyper-prolactinemia who developed SLE. A survey of premenopausal women whose sera were submitted for autoantibody testing showed that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many hyperprolactinemic patients whose sera were referred to an endocrinology laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE. Disease activity was suppressed in six of seven SLE patients treated with bromocriptine. All had elevated disease activity and five became unexpectedly hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords a means of treating clinical SLE activity.

Bromocriptine↗

Autoantibodies in pet dogs owned by patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is evidence to suggest that the disease is caused by a transmissible factor that may cross the species barrier. We investigated this possibility by looking for autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs owned by patients with SLE and comparing results with those obtained with serum from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune diseases. We used standard immunological assays modified for use with canine samples. Compared with the normal dogs, increased amounts of antibody to double-stranded DNA were found in serum from the SLE patients' dogs (median optical density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum protein electrophoresis patterns were found in samples from the autoimmune and SLE patients' dogs but not the normal dogs. These findings support the idea that exposure to common environmental factors or transmissible agents may have a role in causing SLE.

Animals↗

Haplotype structure of TNFRSF5-TNFSF5 (CD40-CD40L) and association analysis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. The tumour necrosis factor (TNF) superfamily of genes play a central role in immune regulation and have been proposed to be involved in the development of SLE. TNFRSF5 (CD40) falls on 20q11-13, a region linked with SLE in three independent genome-wide studies. TNFSF5 (CD40L) falls on Xq26 and is the ligand for TNFRSF5. Seven single-nucleotide polymorphisms (SNPs) in CD40 and eight SNPs in CD40L were looked at for linkage disequilibrium (LD) and haplotype analysis in European-Caucasians. Limited haplotype diversity was observed across CD40 and CD40L, and >97% of the diversity was captured. We also examined the association of SNPs and haplotypes in CD40 and CD40L with SLE in European-Caucasians. There was no evidence of association for CD40 or CD40L in 408 European-Caucasian families with SLE from UK. Haplotype tagging SNPs (htSNPs) are made known, which will facilitate analysis for susceptibility in other autoimmune diseases and risk for infectious disease.

CD40 Antigens↗