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Systemic Lupus Erythematosus (systemic + lupus_erythematosus)
Kinds of Systemic Lupus Erythematosus Terms modified by Systemic Lupus Erythematosus Selected AbstractsQuinacrine and hydroxychloroquine, a forgotten combination for patients with active systemic lupus erythematosus in Australasia?INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2003Daniel W. T. Ching Abstract In 1994, A 39-year-old Female Patient With Systemic Lupus Erythematosus (Sle) Was Diagnosed As Having Lupus-induced Serositis. She Was Commenced On Hydroxychloroquine (Hcq) And Prednisone. Her Disease Kept Relapsing Whenever She Was Tailed Off Prednisone. In 1997, Quinacrine (Qn) Was Commenced, And Prednisone Was Gradually Stopped. Her Disease Has Remained In Remission On The Combination Of Hcq And Qn. In December 2000 She Ran Out Of Qn For A Week, And Within This Period She Started To Experience Fatigue And Polyarthralgia Again. Quinacrine Is Available From Compounding Pharmacies, And Is Relatively Cheap. The Combination Of Hcq And Qn In The Treatment Of Sle Should Be Considered More Often. [source] Roles of CD147 on T lymphocytes activation and MMP-9 secretion in Systemic Lupus ErythematosusJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2007Gina Pistol Abstract The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 × CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs. [source] Bullous Lupus: An Unusual Initial Presentation of Systemic Lupus Erythematosus in an Adolescent GirlPEDIATRIC DERMATOLOGY, Issue 4 2010Monica Tincopa B.S Autoimmunity in bullous systemic lupus erythematosus is characterized by the presence of circulating anti-type VII collagen antibodies. We report here a case of a child whose initial systemic lupus erythematosus presentation was a diffuse bullous eruption. [source] Papulonodular Mucinosis in a Child with Systemic Lupus ErythematosusPEDIATRIC DERMATOLOGY, Issue 5 2007CLAUDE BACHMEYER M.D. No abstract is available for this article. [source] Shrinking Lung Syndrome in a 14-Year-Old Boy with Systemic Lupus ErythematosusPEDIATRIC PULMONOLOGY, Issue 2 2006Polly J. Ferguson MD Abstract Pulmonary complications occur frequently in people with systemic lupus erythematosus. We report on an adolescent with an acute onset of dyspnea and pleuritic chest pain with severe restrictive lung physiology on pulmonary function testing (forced vital capacity, 20% of predicted) who had no evidence of parenchymal lung or pleural disease. He was found to have restricted diaphragmatic movement as assessed by fluoroscopy, without evidence of generalized respiratory muscle weakness. His clinical presentation and results of diagnostic tests were typical for shrinking lung syndrome. Given the rarity of shrinking lung syndrome in the pediatric age range, many clinicians are not aware of it as a clinical entity. Shrinking lung syndrome should be included in the differential diagnosis of dyspnea in both children and adults with systemic lupus erythematosus. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Systemic Lupus Erythematosus and Breast CancerTHE BREAST JOURNAL, Issue 1 2008Michalis Kontos MD Abstract:, There is evidence that certain connective tissue diseases such as scleroderma are associated with an increased risk of malignancy. Although it has been claimed that systemic lupus erythematosus (SLE) carries an increased risk of breast cancer, review of the available literature suggests that this is not the case, or, any increase is very small. Women with SLE do not need to be under close surveillance for breast cancer. In patients suffering from both SLE and breast cancer, radiotherapy has been regarded as relatively contraindicated because of fears concerning early and late complications. This view is not supported by the available literature and the majority of such cases can be treated by standard breast-conserving therapy, including breast irradiation. [source] Preferential recognition of the phosphorylated major linear B-cell epitope of La/SSB 349,368aa by anti-La/SSB autoantibodies from patients with systemic autoimmune diseasesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006A. G. Terzoglou Summary Sera from patients with primary Sjögren Syndrome (pSS) or Systemic Lupus Erythematosus (SLE) often contain autoantibodies directed against La/SSB. The sequence 349,368aa represents the major B-cell epitope of La/SSB, also it contains, at position 366, a serine aminoacid residue which constitutes the main phosphorylation site of the protein. In this study we investigated the differential recognition of the 349,368aa epitope and its phosphorylated form by antibodies found in sera from patients with systemic autoimmune diseases. Peptides corresponding to the sequence of the unphosphorylated (pep349,368aa) and the phosphorylated form (pep349,368aaPh) of the La/SSB epitope 349,368aa, as well as to a truncated form spanning the sequence 349,364aa and lacking the phosphorylation site (pep349,364aa), were synthesized. Sera from 53 patients with pSS and SLE with anti-La/SSB specificity, 30 patients with pSS and SLE without anti-La/SSB antibodies, 25 patients with rheumatoid arthritis and 32 healthy individuals were investigated by ELISA experiments. Autoantibodies to pep349,368aaPh were detected in sera of anti-La/SSB positive patients with a higher prevalence compared to the pep349,368aa (66%versus 45%). Pep349,368aaPh inhibited the antibody binding almost completely (92%), while pep349,368aa inhibited the binding only partially (45%). Anti-La/SSB antibodies presented a higher relative avidity for the phosphorylated than the unphosphorylated peptide. Immunoadsorbent experiments using the truncated peptide pep349,364aa indicated that the flowthrough showed a selective specificity for pep349,368aaPh, while the eluted antibodies reacted with both peptide analogues of the La/SSB epitope. These data suggest that sera from pSS and SLE patients with anti-La/SSB reactivity possess autoantibodies that bind more frequently and with a higher avidity to the phosphorylated major B-cell epitope of the molecule. [source] Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strainsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2005Liang Ma Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-, and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ- lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a ,butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis. [source] A tolerogenic peptide down-regulates mature B cells in bone marrow of lupus-afflicted mice by inhibition of interleukin-7, leading to apoptosisIMMUNOLOGY, Issue 2 2009Hava Ben-David Summary Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE-afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE-afflicted (New Zealand Black × New Zealand White)F1 mice were largely expanded, and that treatment with hCDR1 down-regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon-, and interleukin (IL)-10], whereas it up-regulated the expression of transforming growth factor-, in the BM. Treatment with hCDR1 up-regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl-xL gene and of IL-7 by BM cells. Furthermore, the addition of recombinant IL-7 abrogated the suppressive effects of hCDR1 on Bcl-xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down-regulated production of IL-7 contributes to the hCDR1-mediated apoptosis of mature B cells in the BM of SLE-afflicted mice. [source] Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosusIMMUNOLOGY, Issue 3 2006Bailin Liang Summary Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from dysregulation of the immune system. Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, monocytes and T and B cells. It stimulates B-cell differentiation/maturation, immunoglobulin secretion, and T-cell functions. Elevated levels of IL-6 in serum, urine and renal glomeruli were detected in patients with active SLE and in murine models of SLE. Our study investigated the role of IL-6 in an SLE-like disease in New Zealand Black/White (NZB/W) F1 mice by administration of an anti-murine IL-6 monoclonal antibody (mAb). Intraperitoneal administration of the anti-IL-6 mAb suppressed the production of anti-dsDNA autoantibody. B-cell proliferation induced by anti-IgM and anti-CD40 was lower in the anti-IL-6 mAb-treated mice, ex vivo studies demonstrated that anti-IL-6 mAb treatment inhibited anti-dsDNA production. Anti-CD3-induced T-cell proliferation and mixed lymphocyte reactions were inhibited by anti-IL-6 mAb treatment, indicating a partial down-regulation of T cells. Histological analysis showed that treatment with anti-IL-6 mAb prevented the development of severe kidney disease. These results suggest that treatment with anti-IL-6 mAb has a beneficial effect on autoimmunity in murine SLE and that autoreactive B cells may be the primary target for anti-IL-6 mAb treatment; its effect on autoreactive T cells is also indicated. [source] Systemic lupus erythematosus with vasculitis confined to the coronary arteriesINTERNAL MEDICINE JOURNAL, Issue 2 2000W. A. C. DOUGLAS No abstract is available for this article. [source] Systemic lupus erythematosus complicated with posterior reversible encephalopathy syndrome and intracranial vasculopathyINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2010Hung-An CHEN Abstract Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic condition characterized by reversible vasogenic edema on neuroimaging. It is associated with various neurological manifestations, including headaches, vomiting, seizures, visual loss, altered mental status and focal neurological deficits. PRES mainly occurs in the setting of eclampsia, hypertension, uremia, malignancy, transplantation, autoimmune diseases and/or use of immunosuppressive drugs. This syndrome has been described in patients with systemic lupus erythematosus (SLE). PRES is a potentially reversible clinical,radiological entity; however, it can be complicated with vasculopathy, infarction or hemorrhage. Vasculopathy has been demonstrated to be a common finding in patients with SLE. We report the case of a woman with lupus nephritis and PRES whose diffuse vasculopathy was present on initial neuroimaging. Subsequent brain computed tomography scan demonstrated interval development of intraparenchymal hemorrhage and subarachnoid hemorrhage. To our knowledge, this unique brain image pattern has not been reported in SLE patients. [source] Innate immunity and systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2006Ou JIN Abstract Innate immunity is the first-line host defence against pathogens and damaged host cells, and the major cellular components are phagocytes such as monocytes/macrophages, polymorphonuclear cells and dendritic cells. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the loss of tolerance to self-antigens, the source of which has been suggested to be apoptotic cells. In this article, we will review studies on apoptosis in SLE and discuss the contribution of innate immunity abnormalities in the development of this condition. [source] Possible coexistence of SLE and sarcoidosis in a Chinese female patientINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2003K. K. Lee Abstract Systemic lupus erythematosus (SLE) and sarcoidosis, both being multisystem disorders, share some common clinical features. However, while SLE is not an uncommon disease in the Chinese population, sarcoidosis is distinctly rare in the Chinese. We report a Chinese female patient whose presenting features tend to suggest a lupus-like illness. However, eventually, the diagnosis of sarcoidosis was documented, based on the histological findings of her lymph node biopsy. The possible coexistence of SLE and sarcoidosis is discussed. [source] Haemolytic uraemic syndrome: An overview (Review Article)NEPHROLOGY, Issue 3 2006IRADJ AMIRLAK SUMMARY: Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children. The syndrome is defined by triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure (ARF). Incomplete HUS is ARF with either haemolytic anaemia or thrombocytopenia. HUS is classified into two subgroups. Typical HUS usually occurs after a prodrome of diarrhoea (D+HUS), and atypical (sporadic) HUS (aHUS), which is not associated with diarrhoea (D,HUS). The majority of D+HUS worldwide is caused by Shiga toxin-producing Esherichia coli (STEC), type O157:H7, transmitted to humans via different vehicles. Currently there are no specific therapies preventing or ameliorating the disease course. Although there are new therapeutic modalities in the horizon for D+HUS, present recommended therapy is merely symptomatic. Parenteral volume expansion may counteract the effect of thrombotic process before development of HUS and attenuate renal injury. Use of antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs should be avoided during the acute phase. Prevention is best done by preventing primary STEC infection. Underlying aetiology in many cases of aHUS is unknown. A significant number may result from underlying infectious diseases, namely Streptococcus pneumoniae and human immunedeficiency virus. Variety of genetic forms include HUS due to deficiencies of factor H, membrane cofactor protein, Von Willebrand factor-cleaving protease (ADAMTS 13) and intracellular defect in vitamin B12 metabolism. There are cases of aHUS with autosomal recessive and dominant modes of inheritance. Drug-induced aHUS in post-transplantation is due to calcineurin-inhibitors. Systemic lupus erythematosus and catastrophic antiphospholipid syndrome may also present with aHUS. Therapy is directed mainly towards underlying cause. [source] The neuropathology and pathogenesis of systemic lupus erythematosusNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2002N. J. Scolding Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease in which neuropsychiatric involvement occurs in about 50% of patients and carries a poor prognosis. Despite extensive research, the precise mechanisms of nervous tissue injury remain the least well understood. This article summarizes the important clinical neuropsychiatric features of SLE and, reviewing classical histopathological and more recent experimental studies, discusses theories concerning their presumed pathogenesis. The distinctive production of diverse autoantibodies seems to be related to defective clearance of apoptotic cells. Antibody-mediated neural cell injury and rheological disturbances represent the two principal suggested mechanisms of tissue injury. An interplay between these processes, underlying genetic factors, their modification by hormones, complicated by a number of secondary factors, may explain the wide spectrum of features encountered in this disease. [source] Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 2 2010Joshua W. K. Ho Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease that has heterogeneous clinical manifestation with diverse patterns of organ involvement, autoantibody profiles and varying degrees of severity of disease. Research and clinical experience indicate that different subtypes of SLE patients will likely benefit from more tailored treatment regimes, but we currently lack a fast and objective test with high enough sensitivity to enable us to perform such sub-grouping for clinical use. In this article, we review how proteomic technologies could be used as such an objective test. In particular, we extensively review many leukocyte surface markers that are known to have an association with the pathogenesis of SLE, and we discuss how these markers can be used in the further development of a novel SLE-specific antibody leukocyte capture microarray. In addition, we review some bioinformatics challenges and current methods for using the data generated by these cell-capture microarrays in clinical use. In a broader context, we hope our experience in developing a disease specific cell-capture microarray for clinical application can be a guide to other proteomic practitioners who intend to extend their technologies to develop clinical diagnostic and prognostic tests for complex diseases. [source] Systemic lupus erythematosus with lichen planus-like eruptions associated with pericarditisTHE JOURNAL OF DERMATOLOGY, Issue 5 2008Takashi KOBAYASHI No abstract is available for this article. [source] Anti-DNA Antibodies Cross-reacting with Laminin Inhibit Trophoblast Attachment and Migration: Implications for Recurrent Pregnancy Loss in SLE PatientsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000FAISAL QURESHI PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans. METHOD OF STUDY: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6,7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated culture dishes. The cultures were then exposed to a mouse monoclonal anti-DNA/anti-LN-1 antibody, to human polyclonal lupus antibodies cross-reacting with LN-1, a function-blocking polyclonal antibody to LN-1, polyclonal antibodies to CN-IV, or IgG control. RESULTS: The explants attached to LN-1 and CN-IV, but not to uncoated culture dishes. LN-1 promoted migration of trophoblast, whereas CN-IV promoted migration of fibroblast-like cells. Trophoblast attachment and migration were abolished in a dose-dependent manner by all three antibodies to LN-1, but not by antibodies to CN-IV or IgG control. Furthermore, the effect of anti-LN antibodies was abolished by preincubating them with LN-1. CONCLUSIONS: These studies suggest that anti-DNA antibodies cross-reacting with LNs may play a role in early pregnancy failure in SLE patients by interfering with placental implantation. [source] Everyone comes from somewhere: Systemic lupus erythematosus and Epstein-Barr virus induction of host interferon and humoral anti,Epstein-Barr nuclear antigen 1 immunityARTHRITIS & RHEUMATISM, Issue 6 2010John B. Harley First page of article [source] Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patientsARTHRITIS & RHEUMATISM, Issue 6 2010Michelle Perna Objective Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE. Methods One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness. Results Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r2 = 0.616 for homocysteine and r2 = 0.595 for ADMA). Conclusion ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease. [source] Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation studyARTHRITIS & RHEUMATISM, Issue 10 2009Jason W. Bauer Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines. These chemokines were associated with more-severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN-regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally. Methods To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFN,-inducible 10-kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3,) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits). Results Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10,10), rising at the time of SLE flare (P = 2 × 10,3) and decreasing as disease remitted (P = 1 × 10,3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ,4 were predictive of lupus flare over the ensuing year (P = 1 × 10,4). Conclusion Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision-making. [source] Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17ARTHRITIS & RHEUMATISM, Issue 8 2009Justin H. Fransen Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting. Methods The uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC-induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme-linked immunosorbent assay. Results DCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin-6 (IL-6) and tumor necrosis factor , production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb,induced DC maturation was shown to be independent of Toll-like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb-matured DCs induced production of IL-2, interferon-,, and, in particular, IL-17, suggesting a Th1/Th17 response. Conclusion Apoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb,induced DC maturation represents an important driving force in the autoimmune response in SLE. [source] Systemic lupus erythematosus: A matter of life and deathARTHRITIS & RHEUMATISM, Issue 6 2009David S. Pisetsky First page of article [source] High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groupsARTHRITIS & RHEUMATISM, Issue 4 2009Bahram Namjou Objective Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. Methods Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case,control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. Results We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 × 10,25). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. Conclusion Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets. [source] Deficiency of the type I interferon receptor protects mice from experimental lupus,ARTHRITIS & RHEUMATISM, Issue 11 2007Dina C. Nacionales Objective Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of type I interferon (IFN-I),stimulated genes (ISGs). The role of IFN-I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN-I signaling in the pathogenesis of murine lupus induced by 2,6,10,14-tetramethylpentadecane (TMPD). Methods IFN-I receptor,deficient (IFNAR,/,) 129Sv mice and wild-type (WT) 129Sv control mice were treated intraperitoneally with TMPD. The expression of ISGs was measured by real-time polymerase chain reaction. Autoantibody production was evaluated by immunofluorescence and enzyme-linked immunosorbent assay. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence. Results Increased ISG expression was observed in the peripheral blood of TMPD-treated WT mice, but not in the peripheral blood of TMPD-treated IFNAR,/, mice. TMPD did not induce lupus-specific autoantibodies (anti-RNP, anti-Sm, anti,double-stranded DNA) in IFNAR,/, mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR,/, mice, proteinuria and glomerular hypercellularity did not develop, whereas these features of glomerulonephritis were found in the TMPD-treated WT controls. The clinical and serologic manifestations observed in TMPD-treated mice were strongly dependent on IFNAR signaling, which is consistent with the association of increased expression of ISGs with lupus-specific autoantibodies and nephritis in humans. Conclusion Similar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD-induced lupus. This lupus model is the first animal model shown to recapitulate the "interferon signature" in peripheral blood. [source] Chimerism occurs twice as often in lupus nephritis as in normal kidneysARTHRITIS & RHEUMATISM, Issue 9 2006Idske C. L. Kremer Hovinga Objective Systemic lupus erythematosus (SLE) is an immune-mediated disease that particularly affects the kidneys, causing lupus nephritis. In experimental mouse models, lupus nephritis can be mimicked by inducing a chimeric state through the injection of parental T cells in offspring. In humans, pregnancy-induced chimerism may play a role in the pathogenesis of autoimmune diseases such as SLE, but it is likely that only certain chimeric cells have pathogenic potential. In this study, we investigated whether the distribution of chimeric cells is different in the kidneys of women with SLE from that in normal kidneys, and we examined the phenotype of chimeric cells in women with SLE. Methods The presence of chimeric cells was investigated by in situ hybridization targeting the Y chromosome in 57 renal biopsy samples from 49 women with lupus nephritis. Fifty-one kidney autopsy specimens without histomorphologic lesions served as controls. Double-staining for the Y chromosome in combination with CD3 and CD34 markers was performed in 5 kidney specimens with lupus nephritis to identify the phenotype of the chimeric cells. Results Y chromosome,positive cells were found in 27 of 49 patients with lupus nephritis and in 13 of 51 normal controls (P < 0.01). Both CD3+ and CD34+ chimeric cells were identified in lupus nephritis kidney specimens. Conclusion Chimeric cells are present significantly more often in kidneys with lupus nephritis than in normal kidneys, and some of these chimeric cells are T cells. This finding is interesting in light of experimental models demonstrating that lupus nephritis is initiated by chimeric T cells. [source] Systemic lupus erythematosus in a multiethnic US cohort: XXXIV.ARTHRITIS & RHEUMATISM, Issue 6 2006Deficient mannose-binding lectin exon 1 polymorphisms are associated with cerebrovascular but not with other arterial thrombotic events Objective To study the association between deficient mannose-binding lectin (MBL) genotypes and arterial thrombotic events in systemic lupus erythematosus (SLE). Methods Patients with SLE of Hispanic, African American, and Caucasian ethnicity from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Arterial thrombotic events (myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene, or tissue loss and/or peripheral arterial thrombosis) that occurred after diagnosis were recorded. Genotyping for MBL gene polymorphisms was performed and their distribution was compared between patients who did and did not have thrombotic events. Results There were 58 events (21 cardiovascular, 27 cerebrovascular, and 10 peripheral vascular) in 48 patients. Patients who had thrombotic events were older and were more likely to be smokers, to have more severe disease, and to have accrued more damage overall. Also, a larger proportion of these patients had C-reactive protein values in the highest quintile of distribution. No significant difference in arterial thrombotic events was found in patients homozygous for MBL-deficient alleles compared with others. Similar results were seen within ethnic groups. Caucasians who developed potential thrombotic events exhibited a higher frequency of MBL-deficient alleles, but the difference was not statistically significant for all events together or for cardiovascular and cerebrovascular events combined. However, when only the cerebrovascular events were considered, the difference became statistically significant. Conclusion Age, smoking, and measures of activity and damage were associated with arterial thrombotic events in patients with SLE, but MBL-deficient genotypes were not, with cerebrovascular events in Caucasians being the exception. The relationship between MBL-variant alleles and arterial thrombotic events may exist only within select ethnic groups and event types. [source] Lupus-like disease and high interferon levels corresponding to trisomy of the type I interferon cluster on chromosome 9pARTHRITIS & RHEUMATISM, Issue 5 2006Haoyang Zhuang Objective Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFN, treatment. This study looked for evidence of autoimmunity in a pedigree consisting of 4 family members with a balanced translocation 9;21 and 2 members with an unbalanced translocation resulting in trisomy of the short (p) arm and part of the long (q) arm of chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster. Methods Subjects were evaluated clinically and serologically for autoimmune disease. Expression levels of IFN,4, IFN,, the type I IFN,inducible gene Mx1, the type I IFN receptor, interleukin-6, and tumor necrosis factor , were determined by real-time polymerase chain reaction. Circulating plasmacytoid dendritic cells, the main IFN-producing cells, were quantified by flow cytometry. Results Both subjects with trisomy of chromosome 9p had a lupus-like syndrome with joint manifestations and antinuclear antibodies: one had anti-RNP and antiphospholipid autoantibodies, and the other had anti,Ro 60. The 3 family members with a balanced translocation 9;21 had no clinical or serologic evidence of autoimmunity, similar to that in relatives who were unaffected by the chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of IFN,/, (comparable with those found in patients with SLE), increased signaling through the IFN receptor (as indicated by high Mx1 expression), and low levels of circulating plasmacytoid dendritic cells (as observed in patients with SLE) were evident. These abnormalities were not seen in individuals with a balanced translocation. Conclusion Trisomy of the type I IFN cluster of chromosome 9p was associated with lupus-like autoimmunity and increased IFN,/, and IFN receptor signaling. The data support the idea that abnormal regulation of type I IFN production is involved in the pathogenesis of SLE. [source] Systemic lupus erythematosus in a multiethnic US cohort: Clinical features, course, and outcome in patients with late-onset diseaseARTHRITIS & RHEUMATISM, Issue 5 2006Ana M. Bertoli Objective To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE). Methods A nested case,control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age ,49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self-reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late-onset lupus, damage accrual, and mortality as dependent variables were then performed. Results Two hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late-onset lupus was an independent predictor of damage accrual (t -test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98,141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07,37.56) (P < 0.001). Conclusion Patients with late-onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early-onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients. [source] | ||||||||||||||||||||||||||||||||||