Systemic Lupus Erythematosus Syndrome Research Articles

AIM2 Facilitates the Apoptotic DNA-induced Systemic Lupus Erythematosus via Arbitrating Macrophage Functional Maturation

Lupus nephritis, a major cause of morbidity in patients with systemic lupus erythematosus (SLE), is generally thought to be induced by macrophage-mediated inflammation following deposition of various autoantibodies in kidneys. We previously reported that macrophage aberrant activation induced by activated lymphocyte-derived apoptotic DNA (apopDNA) have been found to play pathogenic roles in the immunodysregulation in lupus nephritis. However, DNA sensor(s) involved in apopDNA-induced macrophage activation and lupus nephritis remains largely undefined. Herein, we aimed to reveal the DNA sensor(s) involved in SLE disease. Correlation between the level of absent in melanoma 2 (AIM2), a cytoplasmic DNA receptor in the inflammasome pathway, and the clinical severity of SLE disease were analyzed in SLE patients as well as in lupus mice. Activated macrophages induced by apopDNA were analyzed by real-time PCR and western blot for AIM2 expression. After silencing of AIM2 via siRNA-mediated knockdown in vitro and in vivo, macrophage activation, inflammatory response, and SLE syndrome were assessed. AIM2 expression was closely correlated with the severity of disease in SLE patients and in lupus mice. Importantly, AIM2 expression was significantly increased in apopDNA-induced macrophages and closely correlated with macrophage activation. Knockdown of AIM2 significantly blunted apopDNA-induced macrophage activation. Furthermore, blockade of AIM2 expression notably ameliorated SLE syndrome via impeding macrophage activation and dampening inflammatory response in apopDNA-induced lupus mice. Our results implied that AIM2 might act as an important DNA sensor and a potential biomarker for apopDNA-induced macrophage functional maturation and SLE disease.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: pooled analysis of the literature reviews and report of six new cases

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder which is increasingly recognized to occur in systemic lupus erythematosus (SLE). The purpose of this study was to identify the characteristics of SLE patients with PRES and the associated factors of the poor outcome among them. We investigated SLE patients who developed PRES between 2005-2011 at the Universiti Kebangsaan Malaysia Medical Centre. A comprehensive literature search was done to find all published cases of PRES in SLE. Pooled analysis was conducted to identify the factors associated with poor outcome. There were 103 cases of PRES in SLE published in the literature but only 87 cases were included in the analysis in view of incomplete individual data in the remaining cases. The majority of the cases were Asians (74.2%), female (95.4%) with mean age of 26.3 ± 8.8 years. PRES was highly associated with active disease (97.5%), hypertension (91.7%) and renal involvement (85.1%). We found that 79 patients had a full recovery (90.8%) with a mean onset of full clinical recovery in 5.6 ± 4.1 days. On univariate analysis and logistic regression analysis the predictors of poor outcome, defined as incomplete clinical recovery or death, were intracranial hemorrhage, odds ratio (OR) 14 (1.1-187.2), p=0.04 and brainstem involvement in PRES, OR 10.9 (1.3-90.6), p=0.003. Intracranial hemorrhage and brainstem involvement were the two important predictors of poor outcome of PRES. Larger prospective studies are needed to further delineate the risk of poor outcome among them.

Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex are associated with psychiatric syndromes in systemic lupus erythematosus: a retrospective study

Objectives: We assessed the association between serum autoantibodies against the 70-kDa polypeptide of the U1-ribonucleoprotein (RNP) complex (U1-70k) and the central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) patients.Methods: We studied 106 hospitalized patients with active SLE, comparing those with (n = 32) and without (n = 74) CNS syndromes. CNS syndromes were further classified into neurologic (n = 21) and psychiatric (n = 15) disorders. Immunoglobulin G (IgG) anti-U1-70k antibodies were measured by enzyme-linked immunosorbent assay (ELISA) using recombinant antigens. IgG antibodies against whole U1-RNP were measured using commercial ELISA kits.Results: Although there was no significant difference in the levels of serum anti-U1-70k antibodies in SLE patients with or without CNS syndromes (p = 0.83), the levels were significantly elevated in SLE patients compared with patients without psychiatric syndromes (p = 0.030). In contrast, no significant difference was observed in the levels of serum anti-U1-RNP antibodies in SLE patients with or without psychiatric syndromes (p = 0.555).Conclusions: These results indicate that serum anti-U1-70k antibodies are associated with psychiatric syndromes in SLE but that they are not associated with CNS syndromes as a whole or with neurologic syndromes. The anti-U1-70k antibodies might be involved in the pathological mechanisms of psychiatric syndromes in SLE.

Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort

Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort

Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities

To evaluate the clinical accuracy of antiphospholipid antibody (aPL) specificities both individually and/or in combination, in a wide cohort of systemic lupus erythematosus (SLE) patients in an attempt to identify a panel of tests that may provide the best accuracy for diagnosing antiphospholipid syndrome (APS). This study included 230 patients (218 women, mean age 42.7 ± 11.9 years, mean disease duration 12.2 ± 8.7 years), all fulfilling the 1982 criteria for SLE. All patients were tested for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-β(2) glycoprotein I (anti-β2GPI), solid phase anti-prothrombin (aPT), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-phosphatidylethanolamine (aPE) antibodies. Sensitivity, specificity and predictive values were calculated. The diagnostic accuracy for each combination of tests was assessed by ROC and their area under the curve analysis as well as by the Youden's index (YI). Testing for six aPL derived 23 possible combinations of results. Among them, LA + anti-β(2)GPI + aPS/PT had the best diagnostic accuracy for APS as a whole and individually for both thrombosis and pregnancy loss (AUC 0.712, OR 3.73 [95% CI 1.82-5.38], P = 0.0001, YI = 0.32 and AUC 0.709, OR 3.75 [95% CI 2.13-6.62], P = 0.0001, YI = 0.37 and AUC 0.677, OR 4.82 [95% CI 2.17-10.72], P = 0.0007, YI = 0.38, respectively) and the best specificity when compared with all the other obtainable combination of tests. Triple positivity for LA + anti-β(2)GPI + aPS/PT was more strongly associated with clinical events (thrombosis and/or PL) when compared with double or single positivity (OR 23.2 [95% CI 2.57-46.2] vs. OR 7.3 [95% CI 2.21-25.97], OR 5.7 [95% CI 2.12-17.01] or OR 3.11 [95% CI 1.56-7.8] for single positivity for LA, aPS/PT and anti-β(2)GPI, respectively). Combining LA, anti-β(2)GPI and aPS/PT improves the diagnostic power and helps in stratifying the risk for each patient, according to their aPL profile.

Mesial temporal lobe epilepsy as a neuropsychiatric syndrome of systemic lupus erythematosus

In this study, we aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunologic profiles of these patients, their seizure and epilepsy classifications, electroencephalography (EEG) and magnetic resonance imaging (MRI) assessments, and the treatment administered for epilepsy and SLE. As the result, 17 patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), eight had epilepsy secondary to stroke, and two had generalized epilepsy. Of the seven patients with MTLE, anteriotemporal spikes were noted in all patients with EEG, and MRI findings suggesting hippocampal sclerosis were noted in four patients. Clobazam and levetiracetam were effective in treating three patients, and one patient underwent amygdalohippocampectomy. In conclusion, MTLE may be a characteristic manifestation of neuropsychiatric syndrome of systemic lupus erythematosus.

Shrinking lung syndrome in systemic lupus erythematosus patients with dyspnea

Aim of the workTo identify the frequency of shrinking lung syndrome (SLS) in systemic lupus erythematosus (SLE) with dyspnea and study the clinical characteristics and differences in disease activity and damage. Patients and methodsThe study included 47 SLE patients complaining of dyspnea. SLS was considered in those with exertional dyspnea, restrictive pulmonary function tests (PFTs) and elevated copula of the diaphragm. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed for all the patients. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) indices were compared. High resolution CT chest was performed for patients with radiological findings consistent with SLS. ResultsThe mean age of the patients was 29.43±7.45years, mean disease duration 5.18±3.62years. The SLS was present in 8 patients (17.02%). There was bilateral elevation of the diaphragm copulae in 25% of SLS patients and two had associated basal atelectatic bands. The serum uric acid was significantly higher in those with SLS while the 24h urine protein was significantly lower and C4 normalized. The levels of SLEDAI and SLICC tended to be lower in those with SLS, yet there was no significant difference from those without. The demographic features, clinical and laboratory manifestations, disease activity and damage scores, PFTs and radiological findings of the SLE patients are presented. ConclusionIn SLE patients with dyspnea, SLS should be looked for as it is present in a high proportion of cases.

Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort

BackgroundThe metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with...

Prévalence et valeur diagnostique des anticorps antinucléaires de spécificité antigénique indéterminée : étude rétrospective à propos d’une série de 90 patients

PurposeThe objective of this study was to determine the clinical relevance and the diagnostic significance of positive antinuclear antibodies (ANA) without identified antigenic target by the usual characterization technique. Patients and methodsRetrospective study conducted in the Laboratory of Immunology of Habib Bourguiba Hospital (Sfax, Tunisia) during 18months. The inclusion criteria were the presence of an ANA titer greater or equal to 1/320 with negative characterization result. ANA screening was performed by indirect immunofluorescence (IIF) on Hep2 cells. Each positive serum was tested by IIF on Crithidia luciliae (anti-native DNA) and by immunodot (anti-nucleosome, anti-histone, anti-Sm, anti-RNP, anti-SSA, anti-SSB, anti-Scl 70, anti-PM-Scl, anti-Jo1, anti-PCNA and anti-ribosomal protein). Sera of systemic lupus erythematosus (SLE), myositis, and scleroderma patients were tested for anti-Ku, anti-PL7, anti-PL12 and anti-Ro-52 using dot myositis. ResultsSera of 90 patients were studied: 18 men and 72 women (average age: 44years). Drug-induced ANA was found in eight patients. The most frequent clinical symptoms were joint (56.7%), cutaneous (54.4%) and constitutional symptoms (45.6%). The diagnosis of an autoimmune disease was suspected in 49 patients (54.5%) and confirmed in 30 (33.3%) including 20 cases of connective tissue disease: myositis (n=6), scleroderma (n=5), Sjögren's syndrome (n=3), SLE (n=4), rheumatoid arthritis (n=6) and antiphospholipid syndrome (n=4). Other autoimmune diseases were less frequent. The anti-Ku antibody was detected in the majority of patients with connective tissue disease. The diagnosis of non-autoimmune diseases was established in 25.5% of patients. Eighteen patients (20%) had no diagnosis orientation. ConclusionOur study demonstrated the diagnostic value of the presence of ANA even in the absence of known antigenic target, confirmed the role of the IIF as “gold standard” test for ANA screening, and suggested the usefulness of the addition of Ku antigen in the immunodot classic profile.

Abstract 223: Acute Ischemic Stroke in a 23-Year-Old Patient with Verrucous Endocarditis, Prothrombin Heterozygote Mutation, and a Patent Foramen Ovale: A Case Report and Literature Review

Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. Since the etiology of stroke in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report a case of acute ischemic stroke in a 23 year-old patient with multiple risk factors. Case Report A 23 year-old Spanish female with a history of tobacco abuse was brought to the Emergency room after she had a sudden onset of left-side weakness, slurring of speech, and lost of consciousness for a couple of minutes. Physical examination: left upper and lower extremities were completely flaccid with left facial weakness. MRI of head confirmed a right middle cerebral artery regional acute ischemic stroke. Transesophageal Echocardiogram revealed small granular densities on the mitral leaflets that consistent with atypical verrucous endocarditis and a patent foramen ovale (PFO). Hypercoagulable evaluation confirmed prothrombin gene mutation heterozygote. The erythrocyte sedimentation rate (ESR) was 75 mm/hour. All other tests were either negative or in normal range. Anticoagulation therapy was started with Heparin and then switched to Coumadin with an INR target of 2.5. Aspirin was also initiated. Discussion The differential diagnosis in young people (under 50 years) for potential etiology of ischemic stroke is broader than that for older adults. Atypical causes are more prevalent in this population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease. Verrucous endocarditis is small thrombotic and nonbacterial lesions on the heart valves and endocardium, occurring frequently in systemic lupus erythematosus (SLE). However, hypercoagulable states and malignancy are often associated with the formation of verrucous endocarditis. Lesions are usually clinically silent. An embolic stroke may be the first feature to suggest the diagnosis. Since there was no evidence in malignancy, SLE, and antiphospholipid syndrome for our patient, hypercoagulable states should be considered as one of the risks for verrucous endocarditis. About 1-2% of the general population is heterozygous for the prothrombin gene mutation. In contrast, in Spain rates of 6% have been reported. It carries a 2 to 4 times increase in venous thrombosis and also increases the risk of arterial thrombosis (stroke and heart attack). Additionally, studies also show that inherited thrombophilic disorders in the pathogenesis of ischemic stroke might relate to congenital heart diseases such as Prothrombin G20210A variant and Factor V Leiden G1691A mutation might be associated with PFO. The prevalence of PFO in patients who have stroke of unknown cause may be about 40%. PFO also increases the rate of paradoxical thromboembolic stroke. This is particularly true in patients who have had a stroke at an age less than 50 years. Since our patient presents multiple risks for recurrent ischemic stroke, life-long anticoagulant therapy should be considered. Conclusion Acute ischemic stroke in a 23-years-old patient with verrucous endocarditis, prothrombin heterozygote mutation, and a PFO, but absent SLE has been rarely reported. Beside, the authors conclude that hypercoagulable testing and echocardiogram should be performed in young patients with stroke in order to provide us a better understanding of the etiology and the best treatment options.

Could Increased Vascular Endothelial Growth Factor Induced by Interleukin 17 Be the Cause of Posterior Reversible Encephalopathy Syndrome in Systemic Lupus Erythematosus?

To the Editor: We read with interest the contribution by Varaprasad, et al 1. They studied patients with systemic lupus erythematosus (SLE) and posterior reversible encephalopathy syndrome (PRES) and suggested that PRES occurs in young patients with lupus at the early stage of the disease. However, they did not explain the exact mechanism of the disease. We would like to add the possible pathomechanism in the development of PRES in SLE. PRES is an uncommon condition that … Address correspondence to Dr. J.I. Shin, 250 Seongsan-ro, Seodaemun-gu, CPO Box 8044, Department of Pediatrics, Yonsei University College of Medicine, Seoul 120-752, Korea. E-mail: shinji{at}yuhs.ac

Off-label use of rituximab in a general hospital

BackgroundThe therapeutic indications for rituximab are: Hodgkin's lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis.PurposeThe aim of this study was to review the off-label use of rituximab in our hospital.Materials and...

Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex are associated with psychiatric syndromes in systemic lupus erythematosus: a retrospective study

We assessed the association between serum autoantibodies against the 70-kDa polypeptide of the U1-ribonucleoprotein (RNP) complex (U1-70k) and the central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) patients. We studied 106 hospitalized patients with active SLE, comparing those with (n=32) and without (n=74) CNS syndromes. CNS syndromes were further classified into neurologic (n=21) and psychiatric (n=15) disorders. Immunoglobulin G (IgG) anti-U1-70k antibodies were measured by enzyme-linked immunosorbent assay (ELISA) using recombinant antigens. IgG antibodies against whole U1-RNP were measured using commercial ELISA kits. Although there was no significant difference in the levels of serum anti-U1-70k antibodies in SLE patients with or without CNS syndromes (p=0.83), the levels were significantly elevated in SLE patients compared with patients without psychiatric syndromes (p=0.030). In contrast, no significant difference was observed in the levels of serum anti-U1-RNP antibodies in SLE patients with or without psychiatric syndromes (p=0.555). These results indicate that serum anti-U1-70k antibodies are associated with psychiatric syndromes in SLE but that they are not associated with CNS syndromes as a whole or with neurologic syndromes. The anti-U1-70k antibodies might be involved in the pathological mechanisms of psychiatric syndromes in SLE.

Bloqueo aurículo-ventricular congénito completo y anticuerpos maternos anti-Ro positivos

Congenital heart block is a rare anomaly produced by an injury to the specialized cardiac conducting tissue, with secondary alterations in the transmission of stimuli from the atria to the ventricles. This defect can be associated with structural heart disease and maternal autoimmune diseases such as systemic lupus erythematosus syndrome or the presence of anti-Ro and anti-La autoantibodies. Prenatal diagnosis is given by echocardiography, which shows persistent fetal bradycardia, and allows detection of fetal hemodynamic deterioration, requiring finalization of pregnancy.Intrauterine therapy consists of sympathomimetics and steroid agents and a pacemaker can be implanted in the newborn as a definitive treatment at the end of the pregnancy.We report the case of an asymptomatic mother at week 26 of pregnancy who presented to the emergency department with abdominal pain. On examination, an anomalous fetal heart rate was detected and congenital heart block was confirmed. The only abnormal result of maternal blood test was the presence of positive anti-nuclear antibodies and anti-Ro autoantibodies.

B Cell-Derived IL-10 Does Not Regulate Spontaneous Systemic Autoimmunity in MRL.FaslprMice

B cells contribute to the pathogenesis of chronic autoimmune disorders, like systemic lupus erythematosus (SLE), via multiple effector functions. However, B cells are also implicated in regulating SLE and other autoimmune syndromes via release of IL-10. B cells secreting IL-10 were termed "Bregs" and were proposed as a separate subset of cells, a concept that remains controversial. The balance between pro- and anti-inflammatory effects could determine the success of B cell-targeted therapies for autoimmune disorders; therefore, it is pivotal to understand the significance of B cell-secreted IL-10 in spontaneous autoimmunity. By lineage-specific deletion of Il10 from B cells, we demonstrated that B cell-derived IL-10 is ineffective in suppressing the spontaneous activation of self-reactive B and T cells during lupus. Correspondingly, severity of organ disease and survival rates in mice harboring Il10-deficient B cells are unaltered. Genetic marking of cells that transcribe Il10 illustrated that the pool of IL-10-competent cells is dominated by CD4 T cells and macrophages. IL-10-competent cells of the B lineage are rare in vivo and, among them, short-lived plasmablasts have the highest frequency, suggesting an activation-driven, rather than lineage-driven, phenotype. Putative Breg phenotypic subsets, such as CD1d(hi)CD5(+) and CD21(hi)CD23(hi) B cells, are not enriched in Il10 transcription. These genetic studies demonstrated that, in a spontaneous model of murine lupus, IL-10-dependent B cell regulation does not restrain disease and, thus, the pathogenic effects of B cells are not detectably counterbalanced by their IL-10-dependent regulatory functions.

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by widespread immunologic abnormalities and multiorgan involvement including the skin, joints, and kidney as well as the peripheral and central nervous systems. The clinical course of SLE is usually dependent on the organ involved such as neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), lupus nephritis (LN), lupus pancreatitis (LP), and pulmonary hypertension (PH). Early diagnosis and epoch-making therapeutic strategies are prerequisites for improved prognosis of patients with SLE. To fulfill this medical need, a better understanding of the pathogenesis of SLE is required. Research over the course of several years has yielded a basic scientific understanding of SLE pathogenesis. This includes understanding the role of various cytokines and chemokines in disease progression, the chronic activation of plasmacytoid dendritic cells by circulating immune complexes, and the expression of neutrophil-specific genes.

Chorea as a First Manifestation in Young Patients with Systemic Lupus Erythematosus who Was Initially Diagnosed with Rheumatic Fever

Chorea is a rare manifestation of systemic lupus erythematosus (SLE). We report on a young patient with chorea who was diagnosed initially with rheumatic fever. Follow up and further evaluation confirmed the diagnosis of SLE and anti-phospholipid syndrome. Of special interest were the negative antiphospholipid (aPL) antibodies and the initial diagnosis of rheumatic fever which is still not uncommon problem in our region. The rarity of such presentation with joint and non specific increase of antistreptolysin O (ASO) titer might be the factors that led to an incorrect diagnosis. Early diagnosis and treatment of SLE and anti-phospholipid syndrome are very crucial and should be considered with such presentation.

The autoimmune tautology: an in silico approach.

There is genetic evidence of similarities and differences among autoimmune diseases (AIDs) that warrants looking at a general panorama of what has been published. Thus, our aim was to determine the main shared genes and to what extent they contribute to building clusters of AIDs. We combined a text-mining approach to build clusters of genetic concept profiles (GCPs) from the literature in MedLine with knowledge of protein-protein interactions to confirm if genes in GCP encode proteins that truly interact. We found three clusters in which the genes with the highest contribution encoded proteins that showed strong and specific interactions. After projecting the AIDs on a plane, two clusters could be discerned: Sjögren's syndrome—systemic lupus erythematosus, and autoimmune thyroid disease—type1 diabetes—rheumatoid arthritis. Our results support the common origin of AIDs and the role of genes involved in apoptosis such as CTLA4, FASLG, and IL10.

Inflammatory biomarkers and oxidative stress measurements in patients with systemic lupus erythematosus with or without metabolic syndrome

The aims of the present study were to report the frequency of metabolic syndrome in systemic lupus erythematosus (SLE); to verify differences in inflammatory biomarkers and oxidative stress in SLE patients with or without metabolic syndrome; and to assess which metabolic syndrome components are associated with oxidative stress and disease activity. The study included 58 SLE patients and 105 controls. SLE patients were divided in two groups, with and without metabolic syndrome. 41.4% patients met the criteria for metabolic syndrome compared with 10.5% controls. Patients with SLE and metabolic syndrome had significantly raised serum uric acid, C-reactive protein (CRP), lipid hydroperoxides, and protein oxidation when compared with patients with SLE without metabolic syndrome. Lipid hydroperoxides were correlated with CRP, whereas protein oxidation was associated with waist circumference and uric acid. There was a positive association between serum C3 and C4 and glucose and between C3 and CRP. SLE disease activity index (SLEDAI) scores were positively correlated with body mass index (BMI) and waist circumference (WC). In conclusion, SLE patients have a high prevalence of metabolic syndrome and this syndrome directly contributes to increase inflammatory status and oxidative stress. Inflammatory processes, being overweight/obese, and uric acid may favor oxidative stress increases in patients with SLE and metabolic syndrome. C3 and C4 may have a positive acute-phase protein behavior in patients with SLE.

Posterior Reversible Encephalopathy Syndrome in Systemic Lupus Erythematosus with Anti‐Phospholipid Antibodies Treated by Plasma Exchange: A Case Report

Posterior Reversible Encephalopathy Syndrome in Systemic Lupus Erythematosus with Anti‐Phospholipid Antibodies Treated by Plasma Exchange: A Case Report